Effect of Solubility on Polymer Swelling and Drug Release from Modified Release Polyethylene Oxide (PEO) Matrix Tablets (T3158)
H. Li, X. Gu, Faculty of Pharmacy; University of Manitoba

Purpose:  To investigate the effect of drug solubility on polymer swelling behaviours and drug dissolution profiles from modified release PEO matrix tablets using a texture analyzer.

Methods:  A series of modified release PEO matrix tablets were prepared by using Polyox® WSR301 at varying ratios (10-50%) and direct tableting compression. Pseudoephedrine (PED, solubility 565.3 +/- 0.3 mg/ml) or acetaminophen (AMP, solubility 18.9 +/- 0.3 mg/ml) was incorporated into the tablets as the model compounds. In vitro dissolution of the tablets was conducted using the USP Apparatus 2. The thickness of gel formation during drug dissolution was recorded using a texture analyzer. Relationship among gel layer thickness, PEO ratio, drug solubility and dissolution was correlated and interpreted.

Results:  Drug dissolution and gel formation were directly proportional to drug solubility and PEO ratio in the matrix tablets. PED released much faster from the formulations than AMP due to its higher aqueous solubility; the time required for 50% of drug release (DT50%) ranged 0.9-1.7 hours for the PED tablets and 6.5 -9.0 hours for the AMP tablets respectively. Diffusion exponent values differentiated significantly between the two preparations, 0.46-0.58 for PED and 0.70 -0.86 for AMP, indicating a diffusion-controlled release mechanism from the PED tablets but an erosion-controlled release mechanism from the AMP tablets. Gel layer thickness of the PED tablets was much larger than that of the AMP tablets; there was a linear correlation between gel layer thickness and PEO proportion used in the tablets.

Conclusions:  Drug solubility and matrix polymer ratio directly affected water penetration into the tablet matrix and polymer gelling formation, subsequently resulting in modified release profiles of PED and AMP. The study demonstrated a unique application of texture analyzer in characterization of tablet formulation and drug dissolution.
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Oral Transmucosal Delivery of Tetrahydrocannabinol and Pro-drugs via Hot-melt Polymeric Matrices: In-vivo Studies in Rabbits (M1176)
M. Munjal1, P. B. Lindgren2, H. C. Fyke2, M. A. ElSohly3, M. A. Repka3
1Department of Pharmaceutics, 2The National Center for Natural Products Research, 3Department of Pharmaceutics, The National Center for Natural Products Research, The University of Mississippi,University, MS 38677

Purpose: To investigate the in-vivo absorption potential of ∆9-Tetrahydrocannabinol (THC) through the buccal route using the rabbit as a model animal.

Methods.: THC and its pro-drugs – hemisuccinate (HS) and hemiglutarate (HG) – were incorporated into polyethylene oxide polymeric matrices using a hot-melt method. Noveon® (bioadhesive) and other excipients were also added to aid in the formation of a stable, bioadhesive delivery system. For the animal studies, these matrices were cut into appropriately sized circular discs containing approximately 5 mg equivalent of THC. The rabbits were sedated with ketamine:xylazine intramuscular injection prior to intubation, and subsequently anesthetized with oxygen and isoflurane gas. Blood samples were collected from the rabbit’s lateral ear artery for up to 5 hrs. The collected blood samples were centrifuged to separate the plasma which was further extracted, derivatized and analyzed for THC and THC-COOH content using GC-MS.

Results: A serum concentration-time curve was constructed upon intravenous injection of an ethanolic solution of THC displaying a rapid decline in drug levels. Upon application of the parent or pro-drug-incorporated polymeric formulation to the rabbit’s buccal pouch area, THC blood levels exhibited high variability. For example, a sharp increase in the THC plasma level was obtained with the THC-HG-loaded matrix in one of the animals, with maximum concentration of 68.7 ng/ml observed at 30 min. Similar formulations of discs containing THC or THC-HS produced plasma concentrations of 11.2 and 4.7 ng/ml, respectively, after 30 min.

Conclusion: Continuous anesthesia of the animals was obtained using the general anesthetic, isoflurane. High plasma vs. time concentrations were obtained for THC following administration of the parent/pro-drug loaded polymeric matrices via the buccal route. However, these plasma-time profiles were determined to be erratic. Studies are ongoing to attain controlledrelease of THC and pro-drugs.
This work was partially funded by NIH grants #1R41 GM067304-01 and # P20RR17701.
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Synergistic or Antagonistic Effect of Binary Combination of Hydrophilic Polymers in Controlled Release (M1216)
L. Li, S. Sethia, S. Gupta, T. Chowdhury, S. Ahmed; Formulation R&D, Barr Laboratories, Inc.

Purpose:  To evaluate the combination effect of binary hydrophilic polymers on drug controlled release by using various methods.

Methods:  The viscoelastic properties of the individual polymer and binary combinations were compared using a TA Rheometer. Viscosity –shear rate profiles of the polymer solutions were measured at various pH conditions. A modified Moisture Sorption Analyzer was used to explore the rate of moisture uptake of the individual and combined polymers at 99% RH. A Texture-Analyzer was used to measure the gel strength of polymer tablets after hydration. Dissolution study was carried out in USP apparatus II for drugs with various degree of solubility.

Results:  Among the polymers evaluated such as HPC, HEC, HPMC, Sodium CMC, Carbopol and their combinations, synergistic combination effect was observed for HPC and Sodium CMC. The viscosity of the HPC/Sodium CMC combination increased approximately 100% relative to individual polymers. However, interestingly, antagonistic effect was observed for HPC and Carbopol. The viscosity dropped about 90% compared to the individual polymers. Combination of HPMC/Carbopol, and HPC/HEC showed no interaction. The gel strength study indicated good correlation with the viscosity changes. However, the moisture uptake method did not correlate with other Methods:  The combination matrixes such as HPC/Sodium CMC and HPC/Carbopol showed synergistic or antagonistic controlled release effect on the dissolution of a highly water-soluble drug.

Conclusion:  In controlled release formulation, combination of two hydrophilic polymers can result in unexpected synergistic or antagonistic effect on polymer gel strength, and further influence the drug release from the polymer matrix. Viscosity measurement and texture analysis are useful methods on studying of the combination effect.
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Analysis of Matrix Geometry and Front Movements for Hydroxypropyl Methyl Cellulose (HPMC), Hydroxypropyl Cellulose (HPC), and Polyethylene Oxide (PEO)(M1220)
S. Missaghi, R. Fassihi; School of Pharmacy, Temple University

Purpose: To compare the swelling and erosion characteristics and drug release properties of extended-release matrix tablets having different size and shape, employing HPMC, HPC, and PEO.

Methods: Three different matrix formulations were prepared using HPMC (MethocelK100M), HPC (KlucelHXF), and PEO (PolyoxWSR303) at 40%w/w, blended with microcrystalline cellulose (40%w/w), tetracycline (19.5%w/w) as a drug marker, and magnesium stearate (0.5%w/w). Tablets were manufactured using direct compression method with two different geometries (500 and 800mg; round and oval). The swelling and erosion characteristics and the release properties of each tablet were investigated in deionized water, using USP 28-appartus II modified with a mesh device, operated at 75 rpm. Tablets were removed at pre-determined time intervals and subjected to textural analysis and cross-sectioning. The extent of water uptake and tablet erosion was evaluated using gravimetrical analysis.

Results: Depending on their composition and geometry, all tablets demonstrated different degrees of swelling and erosion. Initially, PEO-matrices showed the greatest extent of water uptake and axial swelling followed by HPMC and HPC. As for erosion properties, HPC-matrices demonstrated the lowest extent of erosion followed by HPMC and PEO. The cross-sections of tablets at 3 hours exhibited distinct fronts with differentiable gel layer thickness. The inter-relationship between the matrix composition/geometry and its release properties in relation to internal structural changes, as determined with textural analysis, was also investigated.

Conclusions: Dynamics of swelling, erosion, and front movements in matrices having round or oval shape demonstrated disproportional changes in shape, erosion, and swelling in each case. Regardless of original shape, the overall change in aspect ratios during swelling were in the order of HPMC>PEO>HPC, while the extent of drug release from matrices was in the order of PEO>HPMC>HPC. The significance of these effects in relation to change in overall textural properties of each matrix and their erosion characteristics is discussed.
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Design and development of controlled release matrices: modeling release kinetics by texture analysis and response surface methodology (RSM) (M1224)
Y. El-Malah, S. Nazzal
Department of Basic Pharmaceutical Sciences, The University of Louisiana at Monroe, Monroe, LA 71209

Purpose:   The objectives of this study were (1) investigate the effect of carbopol and polyox (Low MW) on release kinetics of theophylline from controlled release matrix tablets, (2) statistically evaluate the effect of polymer blends on dissolution rate by RSM, and (3) develop an optimized tablet with a 12-hour, zero-order release kinetics.

Methods:   The effect of polymer blend on diffusion and swelling kinetics was evaluated using a TA-XTPlus Texture Analyzer. A timerepeat compression model using a modified In-Vitro dissolution assembly was developed and applied for this study. A 3-factor, 3-level D-Optimal design was used to explore the linear and quadratic response surfaces and construct a second order polynomial model. Factors investigated were: low MW Polyox (X1), carbopol (X2), and lactose(X3). Responses were: time to 50% release (Y1), and cumulative percent of drug released after 2, 4, 6, 8, and 12hrs (Y2-Y6). Tablets of variable compositions were compressed at 5000 lb using concave 10mm punches. Dissolution was evaluated in USP Type II apparatus.

Results:  Carbopol concentration showed significant effect (p < 0.05) on the response (Y1). This effect was demonstrated by contour and ternary surface plots. Polyox had marginal effect on dissolution. Polyox effect was apparent on modulating release pattern, which was expressed as the release exponent (n). This effect was further verified from the yield strength values derived from the Texture ¡§force-displacement curves¡¨. RSM predicted optimum levels of X1, X2, and X3 under the constrained dissolution variables: 2hr: 17%, 4hr: 33.3%, 6hr: 50%, 8hr: 66.7%, and 12hr: 100%. A new formulation was prepared according to the predicted levels. Observed responses were 2hr: 21.3%, 4hr: 37.9%, 6hr: 56.7%, 8hr: 76.6%, and 12hr: 99.9%.

Conclusion:  Low MW Polyox plays a critical role in modulating drug release and diffusion from hydrophilic matrices in which carbopol is the primary diffusion controlling polymer.
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In Vitro Performance Characterization of Expandable Tablets using the Texture Analyzer (M1233 )
P. Shao1, J. Wan1, L. Lu2; 1Solids Development- Ann Arbor, Pfizer Global Research and Development, 2Chemical Engineering,University of Michigan

Purpose:  To develop a method to characterize the physical performance (swelling rate and rigidity) of expandable tablets using Texture Analyzer.

Methods:  An experimental expandable tablet formulation was used as a platform to develop a method on the texture analyzer to characterize the swelling rate and rigidity of expandable tablets. The experimental set-up for swelling rate measurement consisted of a mesh stand and agitator placed inside a jacketed beaker maintained at 37ºC. Dry tablets were placed on the mesh stand and the probe was positioned at the center of the tablet. The test was initiated upon the addition of water at 37ºC. For swelling rate determination, a software sequence was written so that the probe will maintain a constant tracking force as the tablet swells by traveling up to accommodate the force buildup. Distance traveled by the probe versus time data was recorded to estimate swelling rate. To characterize rigidity, the probe was programmed to compress down on the tablet at a constant speed until it penetrated the entire height of the tablet. Force versus distance data was recorded to estimate tablet rigidity.

Results:  Swelling profiles were generated for the expanding tablet for different tracking force values. A tracking force of 2g was determined to be optimum for swelling rate determination. Force versus distance data was recorded during rigidity measurement using control tablets at 2 and 4 hour swelling times. Area under the force-distance curve and maximum force experienced by the probe were calculated and compared for different probes at 2 and 4 hour swelling times. A trigger force of 0.5g using the cylinder probe was determined to be optimum for rigidity measurement.

Conclusion: A method was developed to characterize the swelling rate and rigidity of expandable tablets. The method was subsequently applied to different expandable tablet formulations.
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Pre-plasticized vs. simultaneously plasticized ethylcellulose powder for dry polymer powder coating (M1239)
I. Terebesi, R. Bodmeier; College of Pharmacy, Freie Universität Berlin

Purpose:  To compare the suitability of pre-plasticized ethylcellulose powder and micronized ethylcellulose (simultaneous spraying of a plasticizer during coating) in the dry powder coating of pellets for extended drug release applications.

Methods:  Pre-plasticized ethylcellulose powder was prepared by spray-drying Surelease, a commercially available aqueous ethylcellulose dispersion containing medium chain triglycerides (MCT) as plasticizer. The powder (particle size: 3.1±0.6 µm) was used for dry powder coating in a fluidised bed coater. The coated pellets (model drug: chlorpheniramine maleate) were cured and the  drug release (USP paddle apparatus, 37°C, 100rpm, pH 6.8 phosphate buffer) was compared to the release of pellets, which were coated with ethylcellulose powder under the simultaneous spraying of the plasticizer. The plasticizer efficiency was determined with the mechanical properties of ethylcellulose films (texture analyzer).

Results:  The effectiveness of MCT as a plasticizer is comparable to the one of dibutylsebacate and acetylated monoglycerides. A higher plasticizing efficiency was found for plasticizers from the citrate family with acetyltributylcitrate≤ acetyltriethylcitrate≤ triethylcitrate≤ tributylcitrate. Uncured pellets coated with spray-dried Surelease powder had an extended drug release with approximately 85% drug released within 8h. With curing, the limiting release profile was achieved at 60°C/24h or 80°C/30min (with approx. 69% drug release after 8h). Although medium chain triglycerides do not belong to the best plasticizers for ethylcellulose, the drug release was comparable to coatings from pure ethylcellulose with simultaneous plasticizer additions with optimized plasticizer type. At 80°C/2h, all formulations gave the limiting release profile.

Conclusion: Spray-dried Surelease as a pre-plasticized ethylcellulose powder required only mild curing conditions to achieve extended drug release from dry polymer powder coated pellets. The drug release was comparable to the release from pellets coated with pure micronized ethylcellulose powder with simultaneous spraying of the plasticizer.
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Application of Texture Analyzer for Evaluating the Performance of Enteric Coated Tablets (T2201)
A. Higuera, J. Zhu, A. Grill, N. Basu
Preformulation PR&D, Forest Research Institute

Purpose:  To determine tablet size and coating thickness and relate them to enteric coating and drug release characterization of Compound A at Q (NLT 85% released) in dissolution testing as a control of product performance.

Methods:  Both core and tablets enteric coated at various levels (2, 4, 6 & 10% w/w gain) with Eudragit L-50 with core tablets were analyzed for diameter using a TA.XT texture analyzer at a surface detection force of 0.6 gm with a No. 8 stainless steel cylindrical probe. Dissolution testing was conducted using USP apparatus 2 in USP pH=1.2 buffer followed by a medium replacement of USP pH=6.8 buffer. The enteric coating performance was determined by the amount of drug leached in pH=1.2 medium at t=2 hr while drug release characterization was determined by the amount of drug released in pH=6.8 at t=4 hr.

Results:   The tablet sizes of various enteric coated tablets increased as the coating levels increased, except at the low coating level where no differences in diameter were observed between core and coated tablets. In addition, tablets coated at various levels did not meet enteric coating performance requirement by displaying dose dumping at pH=1.2 where tablets coated at much higher levels did not. On the other hand, tablets coated at higher levels demonstrated an incomplete drug release LT85%, which did not reach the desired Q.

Conclusion:  Texture analyzer has been successfully used to measure the coating thickness of the enteric coated tablets, which then will indirectly help predicting the drug release characteristics and the product performance.
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Effect of Gelatin Bloom Strength and Xylitol Addition on Texture Parameters of Chewable Softgel Films (T3153)
H. Nasri, L. Fonkwe, X. Guo, Research & development, Banner Pharmacaps Inc.

Purpose:  The objective of this study is to investigate the influence of gelatin bloom strengths and xylitol addition on moisture retention and texture parameters such as chewiness, hardness, and adhesivenss of the chewable softgel films.

Methods:  Softgel films were made by casting appropriate amounts of the chewable gel masses containing different gelatin grades (60-80, 100 and 150 bloom strengths) or with xylitol at levels between 0% to 10% (w/w) on a Teflon overlay. The Films were dried overnight at room temperature. The thickness of the films was determined by a multiple point measurements using a caliper. The dried films were stored in HDPE Bottles at 40 ^oC and 75% R.H. for 3 months. Samples were taken at pre-determined time points. The moisture content of the films was determined by a moisture analyzer (Computrac Max 1000, Arizona Instrument). The texture analysis was performed to evaluate chewiness, hardness, and adhesiveness of the chewable films using a texture analyzer (TA.XTPlus, Texture Technologies Corp.).

Results:  The thickness of the chewable softgel films was about 0.10 inch. Films with lower bloom strength grade of gelatin appeared more chewable. Moisture analysis showed that xylitol addition increased moisture retention of the films by up to 3% over the control sample (0% xylitol). Texture Analysis showed that increasing the xylitol level from 0.5% to 10% (w/w) resulted in slight improvement of chewiness but increased hardness. Initial stability indicated the possible crystallization of xylitol from the films during storage.

Conclusion: The results of this study revealed that the selection of appropriate bloom strength of gelatin could be essential for the chewability and the possibility of using Xylitol as a mean to enhance moisture retention and chewiness when formulating chewable softgel capsules.
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Effect of Solubility on Polymer Swelling and Drug Release from Modified Release Polyethylene Oxide (PEO) Matrix Tablets (T3158)
H. Li, X. Gu; Faculty of Pharmacy, University of Manitoba
Purpose: To investigate the effect of drug solubility on polymer swelling behaviours and drug dissolution profiles from modified release PEO matrix tablets using a texture analyzer.

Methods: A series of modified release PEO matrix tablets wereprepared by using Polyox® WSR301 at varying ratios (10−50%) and direct tableting compression. Pseudoephedrine (PED, solubility 565.3±0.3 mg/ml) or acetaminophen (AMP, solubility 18.9±0.3 mg/ml) was incorporated into the tablets as the model compounds. In vitro dissolution of the tablets was conducted using the USP Apparatus 2. The thickness of gel formation during drug dissolution was recorded using a texture analyzer. Relationship among gel layer thickness, PEO ratio, drug solubility and dissolution was correlated and interpreted.

Results: Drug dissolution and gel formation were directly proportional to drug solubility and PEO ratio in the matrix tablets. PED released much faster from the formulations than AMP due to its higher aqueous solubility; the time required for 50% of drug release (DT50%) ranged 0.9−1.7 hours for the PED tablets and 6.5−9.0 hours for the AMP tablets respectively. Diffusion exponent values differentiated significantly between the two preparations, 0.46−0.58 for PED and 0.70−0.86 for AMP, indicating a diffusion-controlled release mechanism from the PED tablets but an erosion-controlled release mechanism from the AMP tablets. Gel layer thickness of the PED tablets was much larger than that of the AMP tablets; there was a linear correlation between gel layer thickness and PEO proportion used in the tablets.

Conclusions: Drug solubility and matrix polymer ratio directly affected water penetration into the tablet matrix and polymer gelling formation, subsequently resulting in modified release profiles of PED and AMP. The study demonstrated a unique application of texture analyzer in characterization of tablet formulation and drug dissolution.
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Dynamic Swelling of Superporous Hydrogels under Compression (T3159)
W. Han, H. Omidian, J. Rocca, Lead Optimization, Kos Pharmaceuticals, Inc

Purpose:  The dynamic swelling of superporous hydrogel (SPH) platforms were investigated in simulated gastric fluid (SGF) under different compression forces and temperatures.

Method:  Elastic SPH platforms were synthesized, purified and dried. TA.XT.Plus Texture Analyzer was utilized in this study. A given SPH sample was placed in a weighing dish and subjected to a constant compression force. Then SGF was brought into contact with the SPH. The timer was set to start once the SPH began to swell under compression. Texture Analyzer recorded the relationship of SPH expansion and elapsed time. The study was conducted in a temperature-controlled chamber. With this study, the dimensional swelling ratio was defined as the ratio of the height of the swollen gel to the height of the dried gel.

Results:  The SPH platforms could rapidly swell under compression in SGF and reached their equilibrium swelling capacities within two minutes. Regardless of the swelling medium temperature, the dimensional swelling ratios of 1.6 and 1.4 were obtained when SPH was compressed under 5 grams and 50 grams, respectively. The SPH swelled slower under 50 grams of compression due to its initial dense microstructure. The dynamic swelling properties including equilibrium swelling capacity and swelling rate was similar for the SPHs evaluated at various medium temperatures of 5, 25, and 37 ^oC.

Conclusions:  The dynamic swelling of elastic SPH platform was found compression-dependent and not sensitive to temperature of the swelling medium. This property can potentially be exploited in designing gastroretentive superporous hydrogels and swellable drug delivery systems.
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Physical Characterization of Soft Gelatin Capsules: II. Capsule drying end point, and  mechanical parameters (T3161)
E. Hassan1, S. Gumudavilli2, K. Magee2, D. Goldman2
1Formulation Development and Scientific Affairs, 2Formulation Develeopment and Scientific Affairs, Pharmaceutics International Inc.

Purpose:  To characterize the drying end point of soft gelatin capsules (SGCs), relative to mechanical parameters such as capsule bursting strength, hardness, and elasticity

Methods:  SGCs were manufactured from a 150 bloom bovine gelatin, filled with a polyethylene-glycol-based fill. Capsules were dried under 20% relative humidity at 24°C for 9.5 days. During the drying process, capsule samples were withdrawn periodically and tested for shell and fill moisture content using Computrac moisture analyzer, and Karl Fisher titrator, respectively. Capsule hardness, elasticity, and bursting strength were concurrently measured using a TA.XTPlus Texture Analyzer (Texture Technologies, USA). Correlation between water loss and the mechanical parameters were also investigated.

Results:  While shell moisture content equilibrated to 6% ± 1% after 3days of drying, fill moisture content approached 7% ±1% only at the end of drying. On the other hand, capsule bursting strength reached 50kg (maximum equipment capacity) after 3 days of drying. In addition, capsules showed improved elasticity factor from 0.5 after 3 days of drying to 0.6 at the end of drying time. Among tested parameters, only capsule hardness correlated well with the fill water content and the drying time.

Conclusion:  During capsule drying, loss of water, and gaining of mechanical strength occur simultaneously. After initial drying, moisture at the capsule shell becomes constant, as water from the fill replaces the water evaporated from the shell. Capsule hardness testing can be used as an overall indicator for both capsule drying and the mechanical quality of soft gelatin capsules.
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Physical Characterization of Soft Gelatin Capsules: I. Non-destructive measurement of capsule hardness and elasticity. (T3162)
E. Hassan1, I. Singh2, E. Coutinho2, D. Goldman2
1Formulation Development and Scientific Affairs, 2Formulation Develeopment and Scientific Affairs, Pharmaceutics International Inc.

Purpose:  To develop a quantitative method for determining both hardness and elasticity of soft gelatin capsules.

Methods:  We defined soft gelatin capsule (SGC) hardness (Hx%) as the force required to reduce the capsule diameter by a specified percentage(x%). On the other hand, capsule elasticity was defined as the ratio between the force applied onto the capsule surface during a compression phase, and the resistance exerted by the capsule when that force is released. Thus the elasticity factor was measured as the ratio between the area under the force-displacement curve while applying the force (AUCa) and that exerted while removing the force (AUCr). Hardness and elasticity of Vegetable oil (oil)-filled or polyethylene glycol (PEG)-filled capsules were evaluated using a TA.XTPlus Texture Analyzer (Texture Technologies, Scarsdale, NY), fitted with a TA-4 1.5In.-diameter flat probe traveling 10%, 25% and 50% of capsule diameters.

Results:  Capsules’ hardness ranged from 2.8kg to 30.2kg, with hardness values increasing as the traveling distance increased from 10 to 50%. On the other hand, capsules’ elasticity was reduced from 0.79 for oil-filled capsules tested at a distance equals to10% of capsule diameter, to 0.11 for a polyethylene-glycol-filled capsules tested at distance equivalent to 50% of the capsule diameter. Using same gel mass, oil-filled capsules were consistently softer( less hard) and more elastic than PEG-filled capsules.

Conclusion:  The proposed test methodology provided a quantitative approach to measure a formerly subjective attribute of soft gelatin capsules. This test can be used as an important tool for development of soft gel capsule products.
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Hot-Melt Extruded Blends of Poly(DL-lactide-co-glycolide) 50:50 and Hydrophilic Polymers: Degradation and Mucoadhesion Characterization (T3172)
M. Kaur, D. Flanagan; Pharmaceutics, University of Iowa

Purpose:  To study the effects of hydrophilic polymers such as polyethylene oxide (PEO, MW-1x105), hydroxypropyl cellulose (HPC, MW-1x106 and HPC-LMW, MW-8x104) and hydroxyethyl cellulose (HEC, MW-1x106) on poly(DL-lactideco- glycolide) (PLGA, 50:50, MW-36x103) hydrolysis kinetics in hot-melt extruded polyblends and to characterize their mucoadhesive properties.

Methods:  Binary blends of PLGA with hydrophilic polymers of varying weight fractions (0-100% PLGA) were prepared by hot-melt extrusion. PLGA degradation in polyblend pellets was determined gravimetrically in phosphate buffered saline (PBS, pH 7.4, I= 0.15 or 0.5 at 370C), by measuring medium pH and by gel permeation chromatography (GPC). Polyblends were evaluated for their water absorption properties gravimetrically, as well. Morphologies of fractured polyblend pellet surfaces were observed using scanning electron microscopy (SEM). Mucoadhesion for polyblend films was determined using a TA.XTPLUS texture analyzer in 6% (w/v) mucus solutions.

Results:  Preliminary data suggested PLGA degradation retardation by HPC and PEO in low ionic strength buffer (0. 15). At 0.5 ionic strength, weight loss profiles of PLGA-HPC showed at most 5% loss of HPC even at 50% HPC up to about 10 days; HPC-LMW showed more than 10% loss at HPC compositions >20% whereas PEO and HEC completely leached out at greater than 10% composition. Increased water-uptake coincides with PLGA erosion. GPC analysis showed that high PEO and HPC-LMW compositions decreased PLGA degradation rate by five-fold whereas HPC and HEC decreased the rate by two-fold. SEM micrographs of PLGA-hydrophilic polymers show porosity at > 20% hydrophilic polymer after leaching. Work of mucoadhesion follows the order HPC > PEO ≡ HPC-LMW >HEC at 50% hydrophilic polymer.

Conclusions:  Degradation study results show that all hydrophilic polymers retard PLGA degradation in high ionic strength buffer. Hydroxypropyl cellulose imparts more mucoadhesiveness to PLGA compared to other hydrophilic polymers.
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Investigations into the use of hydrogels as mechanical skin simulants for jet injectors (W4207)
S. Corr1, G. Eccleston1, J. Hempenstall2, N. Hudson3
11Department of Pharmaceutical Sciences, 3Department of Pure and Applied Chemistry, University of Strathclyde, 2Product Development-1 Harlow, Pharmaceutical Development, GlaxoSmithKline

Purpose. To develop mechanistic understanding of jet injection (needle free) into skin by (i) investigating selected hydrogels as mechanical skin simulants and (ii) assessing the suitability of Young’s modulus (in unconfined compression) as a strength measure to correlate hydrogel properties with jet injection parameters in relation to skin in vivo.

Method. Cross-linked polyacrylamide gels (5-30 %w/w) were prepared by in-situ co-polymerisation and gelatin gels (16-52 %w/w) by dissolution of gelatin in water (65°C) and cooling (4°C) to set. Hydrogels prepared as cuboids at a range of dimensions (cross-sectional area, A0, and length, l0). Gel strength parameters in unconfined and confined compression (e.g. apparent Young’s modulus (E) and work of fracture (W)), were determined at room temperature (18°C) for a range of gel dimensions, probe diameter, and probe velocity, v. For visualization experiments, samples of gel samples were injected with dye (0.2 mL of 1.5 mM solution of sulforhodamine B dye) using a commercial jet injector, and penetration characteristics were correlated with gel strength parameters.

Results. Typical data for gelatin: probe diameter, 2 mm; l0, 30 mm; A0, 500 mm2; v, 10-4 ms-1; concentration, 52.3 %w/w:, E, 9.22 ± 0.99 MPa; W, 18.71 ± 5.29 mJ; normalised penetration depth, 0.41 ± 0.09. An increase in E and W and decrease in normalised penetration depth with increasing gel concentration was shown for both gels. The relationship between sample geometry, probe diameter, E and other strength measures (e.g. W) was different for each hydrogel. Both gel types displayed similar visual injection characteristics. Changing probe speed indicated that E did not display rate dependency within the range studied.

Conclusions. Both gels are equivalent as visualization aides. Young’s modulus, as determined by unconfined compression may be a suitable qualitative parameter for jet penetration studies, but may not be quantitatively applied to skin in vivo.
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Effects of Polyethylene Glycol on Characteristics of Gelatin Gel Masses and Films (W4212)
Q. Fang, L. Fonkwe and X. Guo; Research & Development, Banner Pharmacaps Inc., 4125 Premier Drive, High Point, NC 27265

Purpose:  The objectives of this study were to investigate the combined effects of polyethylene glycol (PEG) and Sorbitol Special (SS) on characteristics of gel masses (viscosity, gelling and melting temperatures), and films (glass transition and melting temperatures, mechanical strength and elasticity).

Experimental Methods:  A full factorial experimental design was employed for the study, including four levels of PEG 400 (0, 5, 10, and 15%) and three levels of Sorbitol Special (10, 15 and 20%). Gel masses were prepared and held @ 60 C for 24 hrs. Viscosity, gelling and melting points were determined using an AR 1000 Rheometer with a range of shear rate of 0 to 50/s (TA Instruments, Newcastle, DE). Films were cast and dried overnight. Resiliency tests were conducted on films to evaluate the mechanical strength and elasticity using a Texture Analyzer. Glass transition and melting temperatures of films were determined using a Differential Scanning Colorimeter (DSC) with a heating rate of 5 oC/min. All acquired raw data were analyzed using JMP statistical software (SAS Institute, Inc.).

Results and Discussion:  Viscosity of gel masses decreased by adding more PEG and Sorbitol Special due to the fact that both of them are plasticizers to gelatin. The gelling points increased as more Sorbitol Special was added. Gel melting points were less affected by the amount of PEG and SS added. The glass transition temperature of dried films increased as more SS added; PEG addition didn’t affect Tg significantly (p<0.09). The film melting temperatures decreased as more PEG and SS added (p<0.009). Films containing more PEG and SS were weaker, but more elastic (p< 0.002).

Conclusions:  PEG lowered the melting temperature of gelatin films. This may be the cause for failures of physical stability of PEG-filled softgel capsules under accelerated conditions. Many pharmaceutical softgel capsules are filled with polyethylene glycol (PEG) based liquids. Polyethylene glycol interacts with the gelatin-based shell, causing a variety of physical stability problems, including sticking, softening, and leaking. This study will help understand the interactions, and find ways to avoid the negative effects and take advantage of the positive effects of PEG.
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Effect of Drugs on Properties of Gel mass and Films  (W4215)
K. Madrigal, L. Fonkwe, Q. Fang, X. Guo; Research & development, Banner Pharmacaps Inc.

Purpose:  To investigate the effects of the drug and its loading on the rheological properties of soft gelatin gel masses containing different type of gelatins and the mechanical properties of the films.

Method:  Naproxen sodium and Dextromethorphan HBr were selected as the acidic and basic model drug, respectively. Acid processed (175 Bloom pig skin) or lime-processed (150 Bloom lime bone) gelatin was used. The drug powder was dispersed in a gel mass containing gelatin, glycerin and water. Each drug was evaluated in gel masses containing either gelatin. Drug loading was from 0 to 4% for the basic drug and 0 to 5.0% for the acidic drug. The gel masses were dried to form drug containing films at room temperature. Gel mass rheological properties (viscosity, gelling temperature, melting temperature, storage modulus and gel elasticity) were determined using an AR1000 rheometer. The mechanical properties were measured using a Texture Analyzer.

Results:  The acidic drug did not change the viscosity of pig skin gelatin gel mass but increased the viscosity of the lime processed gelatin gel mass at 5% drug loading. The acidic drug lowered gelling and melting temperatures, gel strength (storage modulus) and gel elasticity in both acid-processed and lime-processed gelatin gel masses. The basic drug seemed to reduce the viscosity of lime-processed gelatin gel mass. In the acid-processed gelatin mass, there was little change in viscosity with drug loading. The basic drug lowered gelling and melting temperatures as well as gel strength (storage modulus). Transparent films were formed for the basic drugs in both gelatins while the acidic drug formed opaque films. The type of drugs and its solubility in the film could modify mechanical properties of the films.

Conclusions:  Drug loading of both acidic and basic drugs caused minimal decrease in viscosity of acid-processed masses compared to lime-processed gelatin. For the acidic drug, some changes in rheological properties were observed. Drug loading affected the mechanical properties of films.
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Characterization of Gelatins from Various Natural Sources (W4218)
L. Fonkwe, K. Sukur, Q. Fang, X. Guo
Research & development, Banner Pharmacaps Inc.

Purpose:  To evaluate and characterize gelatins from various natural sources for applications in soft gelatin capsules.

Method. Limed bovine bone gelatin, limed bovine skin gelatin, limed porcine bone gelatin, acid porcine skin gelatin, fish gelatin and poultry gelatin were selected. Gelatin solutions were prepared in water at concentrations of 15, 30, 45 & 60% (w/w). Each solution was poured into a sample cup and aged for 24 hours at ambient temperature prior to measurements. The gel strength of each gel formed was measured using a TA-XT2 texture analyzer (Texture Technologies Corp.). Rheological properties (viscosity at 60C, gelling temperature, melting temperature storage modulus and elasticity) of each sample were analyzed using an AR1000 rheometer (TA Instrument).

Results:  The viscosities of the different gelatin solutions were similar at the same concentration. Poultry gelatin appeared to have the lowest viscosity at concentrations above 30% while fish and bone gelatin appeared to have slightly higher viscosities. Bovine, porcine and poultry gelatin had similar gelling and melting temperatures which were higher than the gelling and melting temperatures of fish gelatin. The differences of storage moduli (measure of gel strength at 10C) and elasticity of the gels were not significant at the same concentration. An exponential relationship was established between the gelatin concentration and parameters.

Conclusions:  Based on the parameters analyzed, the gelatin from the various sources analyzed could be utilized for soft gelatin capsule manufacturing. The most significant difference observed among the parameters was the lower gelling and melting temperatures of fish gelatin. It may require certain adjustments during soft gelatin capsule manufacturing and may affect some capsule properties.
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Further Investigations of Deliquescence Lowering in Binary Mixtures: Implications of Lowering RH0 in Binary Mixtures (W4242)
A. Salameh, L. Taylor; Industrial and Physical Pharmacy, Purdue University

Purpose. To study the chemical reactivity and mechanical properties of a mixture which exhibits the phenomenon of lowering of the deliquescence point. A further goal was to investigate the eutonic composition of a model API-excipient system.

Methods. Preliminary studies of chemical reactivity utilized sucrose-citric acid system. Water activity (aw) versus time profiles and RH0mix of sucrose-citric acid system were determined. Physical mixtures (50:50 %w/w) of citric acid:sucrose were stored above and below RH0mix to induce concretion. Mechanical testing using a TA analyzer was used to assess the degree of caking. The eutonic composition was prepared by crystallizing a solution saturated with respect to both the model API, diphenhydramine HCl, and sucrose. Raman microscopy was used to map the crystallized phase.

Results. Saturated solutions of sucrose and citric acid had decreasing aw profiles with time indicating that sucrose was being hydrolyzed in the presence of citric acid leading to decreased aw readings. In addition, the same mixture showed a large discrepancy between the RH0 and aw values. Citric acid-sucrose physical mixtures stored below the RH0mix remained free flowing, while mixtures cycled above and below RH0mix formed agglomerates that showed a yield point when crushed using the TA analyzer. Diphenhydramine HCl and sucrose saturated solution crystallized into circular formations. Raman microscopy mapping showed DPH and sucrose crystallized together as an intimate phase.

Conclusion. Preliminary studies indicate that chemical reactivity will be increased in sucrose-citric acid mixtures that are exposed to RH’s higher than RH0mix and significant caking/concretion will be induced by RH fluctuations that exceed RH0mix. From a saturated solution, deliquescent API and excipient tend to crystallize into intimate structures (possibly the eutonic).
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Synchronization of swelling, erosion, and release in a novel and robust formulation of glipizide (W5066)
S. Jamzad, R. Fassihi; School of Pharmacy, Temple University

Purpose:  To develop a robust direct compression monolithic controlled release (CR) matrix formulation for glipizide equivalent to push-pull osmotic pump system Glucotrol XL.

Methods:  Several monolithic matrix formulations were developed for glipizide by blending the drug substance (10mg/tablet) with various types and levels of release modifying ingredients (HPMC and lactose), magnesium stearate, and colloidal silicone dioxide followed by direct compression. Drug release, hydration, and erosion were evaluated in pH 6.8 phosphate buffer at 75rpm using USP 27 dissolution apparatus II modified by insertion of mesh. Textural analysis was performed using TA-XT2i Texture Analyzer and the force-displacement-time profiles at different time points were determined. Similarity factor (f2) and difference factor (f1) were calculated.

Results:  Developed formulations demonstrated linear release profile similar to Glucotrol XL push pull osmotic pump. In these formulations changing the amount and grade of the polymers and lactose within a range of ±20% w/w did not affect the release profiles significantly. The results of hydration and erosion study revealed the linear interdependence of swelling, diffusion, and erosion on drug release kinetics.

Conclusions:  A robust matrix CR formulation for glipizide was developed with linear release profile similar to Glucotrol XL. It was shown that release profile could be maintained within an acceptable range by controlling the degree of swelling/hydration of the matrix. Regardless of the composition of the formulation, linearity of release was fully dependent on synchronization of three parameters namely swelling, erosion and textural properties of the matrix. Changes in the formulation within ±20% w/w of release modifying agents did not change either the drug release kinetics or the synchronization characteristics. The robustness observed can lead to ease of scale-up, successful in-vivo performance, and improved compliance with SUPAC guidelines.
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The development and characterisation of a novel thermosetting, bioadhesive polymer as a platform for drug delivery (W5095)
T. Laverty, D. Jones, G. Andrews; School of Pharmacy, Queen’s University of Belfast

Purpose:  To develop and manufacture a novel thermo responsive bioadhesive gel as a novel drug delivery model.

Methods:  Pluronic (Poloxamer) 407 gels (15, 20, 25 and 30% w/w) were formed via the slow addition of polymer to deionised water at 8°C which were then left to refrigerate at 4°C for 24 hours to ensure complete dissolution and aid the removal of trapped air. Pluronic 20 and 25% w/w were chosen as candidates for further analysis through the introduction of 5 and 10% w/w Gantrez. Rheological analysis was carried out at 32°C and at 4°C using a TA systems AR2000 rheometer with a 4 or 6cm diameter parallel plate geometry or concentric cylinder and a 1mm plate gap, as previously reported (Jones et al. 2001). The mucoadhesive strength was determined by measuring the force required to detach the formulations from a mucin disc using a texture analyser as previously described (Jones et al. 1999). Throughout the study five replicates of each measurement was carried out.

Results:  All formulations were found to exhibit pseudoplastic flow with minimal thixotropy. Interestingly the introduction of gantrez to the 20% pluronic system caused a decrease in viscosity at 32°C the opposite effect was seen when rheological analysis was carried out at 4°C.

Conclusions:  Gantrez interacts with the pluronic structure in some way causing a complementary decrease in viscosity. The interaction between these polymers will require further study before any novel drug delivery system with these polymer mixes are developed.

References:
Jones, D.S., Irwin, C. R., Woolfson, A.D., et al. (1999) J. Pharm. Sci. 88: 592-598.
Jones, D.S., Brown, A.F., Woolfson, A.D. (2001). J. Pharm. Sci. 90(12): 1978-1990.
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In-vitro evaluation of mucoadhesive tablet formulations as potential tools to increase colonic residence time (W5116)
M. McGirr1, M. McAllister2, A. Basit1; 1Department of Pharmaceutics, The School of Pharmacy, 2Strategic Technologies, Pharmaceutical Development, GlaxoSmithKline

Purpose:  To measure the mucoadhesive properties of three tablet formulations containing various grades of Carbopol ®(CP) as a potential tool to increase colonic residence.

Method. TX-20 Texture Analyser was used to measure the Peak Detachment Force (PDF) for the test formulations. CPgrades 974PNF, 971NF and 980NF were evaluated as: i) Mucoadhesive Film coats (0.5-1% weight gain), ii) Direct compression matrix cores (5 and 10% w/w) iii) Wet granulated matrix cores (5 and 10% w/w).Tablet cores were 8mm diameter, 250mg weight. Test tablets were attached to a 20mm diameter Aluminium probe using adhesive and placed in the hydration media, pH 6.8 phosphate buffer, for 1, 2 and 4 minutes. The probe was lowered to create contact between the test material and a glass surface and was held for 1 minute with 2N force before retracting at a speed of 10.0mm/s.

Results:  It was demonstrated that the grade of CP effects mucoadhesive abilities in the order of CP 974PNF > 980NF > 971NF. Type ii formulations exhibit the greatest PDF (1.280N, 5% CP 974PNF, 4 minute hydration) which increase with hydration time. In contrast, type i formulations show significantly lower adhesion (0.118N CP 974PNF 4 minute hydration), this is reduced with hydration time. Comparison of type ii and iii formulations shows the granulation process affects the mucoadhesion of these systems, type iii formulations exhibit reduced adhesion by up to 0.2N after 4 minutes hydration. It was also observed that mucoadhesion increases with increased CP levels.

Conclusions:  We have shown that in all cases mucoadhesive tablet formulations can be made and tested in-vitro, all three systems exhibit mucoadhesive properties with type ii and iii formulations possessing the greatest potential as tools to increase colonic residence time.
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Application of Texture Analysis in Study of Hydrophilic Solvents Compatibility with Hard Gelatin Capsules (W5142)
X. Mei, F. Etzler, Z. Wang; Pharmaceutics, Boehringer Ingelheim Pharmaceuticals, Inc.

Purpose:  To develop and apply a new technology – Texture Analysis for evaluation of hard gelatin capsule compatibility with hydrophilic solvents.

Methods:  Isotherms of empty capsules were generated by incubating the capsules with saturated salt solutions at 25C for at least 20 days. Moisture content was determined by TGA (105C for 16 hours). Individual hydrophilic solvents (ethanol, propylene glycol, PEG 400) or their mixtures in Cremophor EL were manually filled into capsules and stored in a sealed aluminum pouch at 25 C/60% RH or 40C/75% RH for one week or 12 days. The capsules were then emptied and analyzed by Texture Analysis. The tests were conducted using a "Return to Start" test option with a "Force in Tension" mode. Different parameters (i.e. elastic modulus, tensile strength and elongation at break) were calculated with software Texture Exponent 32.

Results:  Capsules with different mechanical properties were quantitatively characterized by Texture Analysis. Both elastic modulus and tensile strength dropped when capsules became softer and weaker with increasing water content. Meanwhile the elongation at break increased dramatically for capsules containing more than 18% water. In contrast, decreasing of moisture content made capsules harder and tougher demonstrated by an increase of elastic modulus as well as tensile strength. When water content dropped below 8%, the capsules became so brittle that the tensile strength and elongation at break started decreasing. It was also demonstrated that ethanol or propylene glycol alone would soften and weaken the capsules. In contrast, capsules filled with pure PEG 400 became hard and tough. Furthermore, strong interactions between propylene glycol and ethanol or PEG 400 were identified.

Conclusions:  A new technology – Texture Analysis which was sensitive, convenient and rapid was developed. The technique was used to evaluate hydrophilic solvents compatibility with hard gelatin capsules.
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Effect of Gelatin Bloom Strength and Xylitol Addition on Texture Parameters of Chewable Softgel Films (W5152)
H. Nasri, L. Fonkwe and X. Guo, Research & Development, Banner Pharmacaps Inc., 4125 Premier Dr., High Point, NC 27265.

Purpose:  The objective of this study is to investigate the influence of gelatin bloom strengths and xylitol addition on moisture retention and texture parameters such as chewiness, hardness, and adhesivenss of the chewable softgel films.

Methods:  Softgel films were made by casting appropriate amounts of the chewable gel masses containing different gelatin grades (60-80, 100 and 150 bloom strengths) or with xylitol at levels between 0% to 10% (w/w) on a Teflon overlay. The Films were dried overnight at room temperature. The thickness of the films was determined by a multiple point measurements using a caliper. The dried films were stored in HDPE Bottles at 40 C and 75% R.H. for 3 months. Samples were taken at pre-determined time points. The moisture content of the films was determined by a moisture analyzer (Computrac Max 1000, Arizona Instrument). The texture analysis was performed to evaluate chewiness, hardness, and adhesiveness of the chewable films using a texture analyzer (TA.XT.Plus, Texture Technologies Corp.).

Results:  The thickness of the chewable softgel films was about 0.10 inch. Films with lower bloom strength grade of gelatin appeared more chewable. Moisture analysis showed that xylitol addition increased moisture retention of the films by up to 3% over the control sample (0% xylitol). Texture Analysis showed that increasing the xylitol level from 0.5% to 10% (w/w) resulted in slight improvement of chewiness but increased hardness. Initial stability indicated the possible crystallization of xylitol from the films during storage.

Conclusion:  The results of this study revealed that the selection of appropriate bloom strength of gelatin could be essential for the chewability and the possibility of using Xylitol as a mean to enhance moisture retention and chewiness when formulating chewable softgel capsules.
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Formulation of a delta-9-tetrahydrocannabinol pro-drug utilizing poly(ethylene oxide) matrices (W5174)
S. Thumma1, M. Repka2; 1Department of Pharmaceutics, 2Department of Pharmaceutics, The National Center for Natural Products Research, School of Pharmacy, The University of Mississippi

Purpose:  To study the effect of molecular weight of poly(ethylene oxide) (PEO) on the bioadhesive properties, release characteristics, and stability of hot-melt casted films containing a pro-drug of delta-9-Tetrahydrocannabinol (THC), THChemiglutarate( HC-HG).

Methods:   A hot-melt casting method was used to prepare PolyOx®PEO polymeric matrices incorporated with 5% THC-HG. Bioadhesive measurements were performed on both placebo polymeric films and those containing the drug (THC-HG) utilizing the TA.XT2i Texture analyzer equipped with a TA-57R probe. The data was analyzed using Texture ExpertTM software. Release studies were performed according to USP 28 apparatus-5, paddle-over-disk method. Film samples were analyzed by HPLC. Stability studies were performed on the films at four different temperature conditions (-18, 4, 25 and 40°C) to determine the % THC-HG remaining for up to 6 months.

Results:  Peak adhesive force and work of adhesion of each of the polymeric matrices was found to increase with an increase in molecular weight of PolyOx®PEO. The presence of THC-HG at a concentration of 5% did not significantly effect the peak adhesive force or work of adhesion of the matrices. Sustained-release of the drug was observed from films containing higher molecular weight PEO (80% drug released from PolyOx®PEO N-750 and PolyOx®PEO WSR1105 in 9hrs and 12 hrs, respectively) while a faster release was observed from the lower molecular weight PEO (100% drug release from PolyOx®PEO N-10 and PolyOx®PEO N-80 in 2 and 3 hrs, respectively). No significant degradation of THC-HG was observed in all of the polymer matrices after one week.

Conclusion:  The results of the present study suggest that lower molecular weight PEO can be optimized, both in terms of bioadhesion and release characteristics, for the mucosal delivery of THC-HG. The studies are relevant to development of a stable bioadhesive transmucosal matrix system for the therapeutic delivery of delta-9-THC.
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Development of Silicone Adhesive Patch containing Clindamycin Phosphate for the Treatment of Acne (R6082)
V. Raul, G. Schalau II, L. Nartker, G. Loubert, J. Cabala, K. Ulman; Life Sciences Healthcare, Dow Corning Corp.

Purpose:  The purpose of this study was to develop a topical patch containing 2, 5 and 10 % w/w of clindamycin phosphate (CP) that would initial display a burst effect followed by steady state drug release. Upon loading with CP, it was important to maintain control of the physicochemical properties, adhesion and cohesion in order to ensure therapeutic effectiveness and wear. It was also critical to confirm the antimicrobial activity of CP in the silicone adhesive matrix.

Methods:  In vitro drug release testing was performed using Franz static diffusion cells. Analysis was completed using a HPLC equipped with a photo-diode array detector at 210 nm. Calibration curve solutions yielded r-values >0.99. Rheological properties, complex viscosity (Eta*), elastic modulus (G’) and the viscous modulus (G”) were each evaluated using a dynamic oscillating rheometer. Adhesion and tack were evaluated using the TA-XTPlus Texture Analyzer (Texture Technologies). Drug particles and drug particle distribution were evaluated using optical microscopy and scanning electron microscopy. Antimicrobial activity was evaluated using zone of inhibition testing using the causative organism of acne, propionibacterium acnes (P. acnes).

Results:  CP drug release was shown to be dependent on the drug-loaded concentration. Acceptable drug release kinetics and content uniformity were demonstrated at all three drug loadings (CP). Drug release profiles confirmed an initial burst effect followed by a steady state release over time. Rheology and texture analyzer results showed evidence that the physicochemical properties of the drug loaded silicone adhesive matrix did not significantly change versus the control adhesive. Microscopy results indicated that drug morphology and size did not change with time. Microbiological testing confirmed the antimicrobial activity of a CP patch using P. acnes.

Conclusion:  Based on physical characterization and drug kinetics results performed during this study, silicone adhesive matrices loaded with 2, 5 and 10 % w/w CP were shown to potentially be effective for the treatment of acne.
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Development and Evaluation of Topical Drug Delivery Patches Formulated with a Silicone Elastomer Gel (R6085)
G. Schalau II, J. Cabala, G. Loubert, V. Raul, X. Thomas; Healthcare Science & Technology, Dow Corning Corporation

Purpose:  To determine the suitability of a novel silicone adhesive as the carrier matrix for a variety of pharmaceutical ingredients in topically-applied drug delivery patches. This new (patent pending) type of adhesive combines the pressure sensitive characteristics and long wearing time associated with viscoelastic silicone adhesives and the elastomeric properties and hurtfree removal of silicone tacky gels.

Methods:  The non-optimized formulations were prepared by blending the pharmaceutical active ingredients with the SSA. The formulations were cast and cured onto a polyester substrate. The physical properties of tack and adhesion were evaluated using a texture analyzer. The release kinetics of the formulations were evaluated using Franz static diffusion cells with complete replacement of receptor solution at specified intervals. Estimation of the amount of active in the receptor solution was performed via UV spectrophotometer or an HPLC equipped with a photodiode array detector.

Results:  Cohesive patches without significantly diminished tack or adhesion were prepared with clobetasol propi