Influence of the components of polymer film on mechanical properties of floating pellets with verapamil hydrochloride in aspect of tableting
Rafal Lunio, Wieslaw Sawicki
Department of Pharmaceutical Technology, Medical University of Gdansk, Hallera 107
80-416 Gdansk, Poland rlun@amg.gda.pl; wsawicki@amg.gda.pl

Mechanical properties of pellets with diffusion film different thickness and plasticizer were investigated. The texture analysis and scanning electron microscopic inspection was carried out. It was found that in the case of using Kollicoat SR 30 D mechanical resistance of pellets more depend on kind than on thickness of film.

Sodium Alginate Drug Delivery Films
Skuli Skulason 1,2, Thordis Kristmundsdottir1, Jon H Thrainsson 1
1 Faculty of Pharmacy, University of Iceland, Reykjavik, Iceland
2 Bio-Gels Pharmaceuticals, Reykjavik, Iceland    skulis@hi.is

Increasing attention to the oral mucosa as a drug delivery route calls for new drug delivery systems and mucoadhesive polymer systems have been research extensively over the last years. Current research looks at sodium alginate in drug delivery films and possibilities of affecting release and adhesion properties.

Evaluation of Sodium-deoxycholate Gels Containing Betamethasone-17-Valerate
Miler Senyiait. Ozeal Ozer
Ege University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 35100, Bornova-Izmir. Turkey     ozgen.ozer@ege.edu.tr

Sodium-deoxcholate (Na-DOC) gels were prepared and their Theological and textural parameters were tested. The elastic moduli and dynamic viscosity value of the gels increased with increasing concentration of Betamethasone-17-Valerate (BMV). Their thixotropic and textural properties were provided additional advantages for dermal delivery of BMV.

Micro Mechanical Investigation of Fracture Properties of Roller Compacted Acetaminophen
Sarsvatkumar Patel 1, Aditya Mohan Kaushal 1,2, Arvind Kumar Bansal 1
1 National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar, Punjab 160062, India.
2 Present Address: Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.   Email: sarsvatpatel@yahoo.com

Mechanical properties of single particles or agglomerates influence a number of pharmaceutical unit operations as well as dissolution and drug release from solid dosage forms. Measurement of single particle mechanical strength is imperative during preformulation stage. The present study was aimed to investigate the fracture behavior of granules of acetaminophen, a high dose and poorly compressible drug.

Hot Tableted Slow Release Pellets With Tramadol Hydrochloride Coated Ethylcellulose Organic Solution And Water Dispersion.
Jaroslaw Mazgalski' 12 ; Wieslaw Sawicki 1
1 Department of Pharmaceutical Technology, Medical University of Gdansk.. 107 Hallera 80-416 Gdansk, Poland
1 , 2  R&D Department.. POLPHARMA Pharmaceutical Works, 19 Pelplinska 83-200 Starogard Gdanski, Poland
mazgalski@amg.gda.pl amg.gda.pl ; wsawicki@amg.gda.pl amg.gda.pl

It has been shown that the mechanical properties of an ethanol solution of ethylocellulose (EC/EtOH) as well as an ethylocellulose (EC) aqueous dispersion (Aquacoat ECD) impacts on the slow release of tramadol hydrochloride (TH) from the tableted pellets. In the process of hot tableting, a very low compression force (1 kN) was used to prevent the EC pellet film coatings from being damaged and to obtain tablets with good physical properties. An additional goal was to obtain a slow release TH from tableted pellets, which would be as similar as possible to the slow release from uncompressed pellets.

Design and Development of Retentive Gastrospheres for the Delivery of Narrow Absorption Window and Low Bioavailable Drugs
Caraqh S. Murphy, Viness Pillay*, Yahya E. Choonara
University of the Witwatersrand, Department of Pharmacy and Pharmacology, 7 York Road, Parktown, 2193, Johannesburg, South Africa.    viness.pillay@wits.ac.za

Retentive gastrospheres were fabricated using an ionic gelification approach with subsequent lyophilisation for the design and evaluation of a drug delivery system intended for the delivery of narrow absorption window and low bioavailable drugs.

Formulation and Evaluation of a Rapidly Disintegrating Oramucosal Wafer Delivery System
Deshika Reddy, Viness Pillay*, and Yahya E. Choonara
University of the Witwatersrand, Department of Pharmacy and Pharmacology, Medical School, 7 York Road, Parktown, 2193, Johannesburg, South Africa   viness.pillay a wits.ac.za

A rapidly disintegrating wafer delivery system was fabricated and subjected to in vitro testing to assess its ability to rapidly and effectively deliver drug to the oramucosa.

Biological Factors Affecting the Bioadhesion Performance of Spheromer III
Edith Mathiowitz 1,2, Meru Nangia 1, Vijayalakshmi Ramanan 1, Katie Rizzolo 1, Tom Sanford 1, James Yeh 1
1 Spherics Pharmaceuticals Inc., 375 Forbes Blvd, Mansfield, MA 02048; emathiowitz@spherics.com
2 Department of Molecular Physiology, Pharmacology, and Biotechnology, Brown University, Providence, RI 02912

Bioadhesion performance of Spheromer™ III  was evaluated using a texture analyzer and porcine intestine as the biological tissue. The region of intestine chosen influenced the bioadhesion. Contact time between the tissue and polymer significantly affected the bioadhesive bond. The bioadhesive strength increased with increase in medium pH and but remain unaffected by changes in ionic strength. Skim milk was found to reduce the bioadhesiveness

Thermosensitive And Mucoadhesive Gels Intended For The Rectal Administration Of Quinine
A.A Koffi1 2 , F. Agnely 1 , A. Makki 1 , G. Tonelli 1 , M. Djabourov 3, K. Bouchemal 1 , G. Ponchel 1 , J.L. Grossiord 1
1 Univ Paris-Sud 11, UMR CNRS 8612. Faculté de Pharmacie. 5, Rue J.B. Clément. 92296 Chatenay-Malabry cedex, France.
2 Univ of Cocody, UFR des Sciences Pharmaceutiques et Biologiques Abidjan, Côte d?Ivoir. 3Laboratoire de Physique Thermique, ESPCI, 10 rue Vauquelin, 75231 Paris cedex 05, France. kawthar.bouchemal@u-psud.fr

The aim of this work was to design thermosensitive and mucoadhesive gels based on a ternary system composed of poloxamer 407, propanediol 1,2 and hydroxypropylmethylcellulose (HPMC) intended for the rectal delivery of quinine in children. This work provides a complete characterization of these systems including rheology, calorimetric and mucoadhesion   measurements as well as in vitro drug release and pharmacokinetics studies.

Comparisons of two in vitro bioadhesion assays: Cahn and texture analyzer
Peter M Cheifetz, Gail Chan, Camilla A Santos(1), Edith Mathiowitz
Department of Molecular Physiology, Pharmacology, and Biotechnology, Brown University, Providence, RI 02912
Peter_Cheifetz@brown.edu; (1)Current Address: Amgen, Inc, West Greenwich, RI 02817

Abstract
Two bioadhesion assays are described; an effort is made to compare and contrast the two methods. One is a unique method focused on small diameter spheres (<1000um). The other uses standard instrumentation and is focused on larger devices. The methods are complimentary and yield insight into the bioadhesive interaction.

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Texture analysis of SLN and NLC based hydrogels
Souto E.B.(1), Müller R.H.(1,2)
(1) Department of Pharmaceutics, Biopharmaceutics and Biotechnology, The Free University of Berlin, Kelchstraße 31, D-12169 Berlin, Germany
(2) PharmaSol GmbH, Blohmstr. 66A, D-12307 Berlin, Germany
e-mail address of presenting author: elianasouto@yahoo.com

Abstract
This study shows the correlation of particle sizes of lipid nanoparticles (SLN and NLC) and adhesive properties of polyacrylate hydrogels containing SLN and NLC.

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In Vitro Assessment Of Bioadhesive Zinc/Polycarboxylate Complexes.
Gemma Keegan1, John Smart(1), Matt Ingram(1), Lara Barnes(1), Gareth Rees(2), Gary Burnett(2).
(1) School of Pharmacy & Biomolecular Sciences, University of Brighton, Moulsecoomb, Brighton BN2 4GJ. UK; G.M.Keegan@brighton.ac.uk
(2) Research & Development GlaxoSmithKline, St George’s Ave, Weybridge, Surrey KT13 0DE. UK

Abstract
In this study zinc/Carbopol 971P complexes were developed for delivery to the oral cavity. The stability, zinc displacement and bioadhesive properties of the complexes were investigated. Results suggest that the complex retains the bioadhesive characteristics of Carbopol 971P and may represent an environmentally responsive oral delivery system beneficial in oral healthcare.

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Highly Plastic Granules for Preparation of Fast-Melting Tablets
Yourong Fu, Kinam Park
Akina, Inc., West Lafayette, IN 47906, U.S.A.
yf@akinainc.com

Abstract
To make fast-melting tablets (FMTs) by direct compression methods, highly plastic granules that can be compressed into tablets at low pressure were developed. The highly plastic granules are composed of three components: porous and plastic materials; optional materials enhancing water penetration; and a wet binder. The porous and plastic nature of the granules allows fast absorption of water into the compressed tablet for fast dissolution of the tablet. The three-component highly plastic granules provide an easy way of making fast melting tablets.

Reliability of Drug Release from Innovative Single Unit Kollicoatâ DDS
K. Meyer and K. Kolter
karl.kolter@basf-ag.de
BASF AG, Development Pharma Ingredients, 67056 Ludwigshafen, Germany

Abstract
Sustained release characteristics as well as the influence of mechanical stress on the new single unit Kollicoatâ DDS was investigated. The delivery system showed a self-repair mechanism and bursting forces of the swollen system greatly exceeding the maximum contraction strength in the human stomach and intestine. Thus, dose dumping should not be a risk.

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Tensile Properties of Ethylcellulose Coatings of a Time-Delayed Oil-Filled Capsule
L.A. Hodges, H.N.E Stevens and A.B. Mullen
Department of Pharmaceutical Sciences, University of Strathclyde, Glasgow G4 0NR, U.K.
h.n.e.stevens@strath.ac.uk

Abstract
Tensile properties of the ethylcellulose coat of our oil-filled capsule affect time delay. Increasing plasticiser concentration decreased tensile stress at break, work done to break film and elastic modulus of the film but increased tensile strain at break. Triacetin-plasticised films exhibited more pronounced effects in comparison to dibutyl phthalate-plasticised films.

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MMP-inhibition; a treatment for oral ulceration
Skuli Skulason1,2, Thordis Kristmundsdottir2, W. Peter Holbrook3.
(1) Bio-Gels Pharmaceuticals Reykjavik Iceland, skulis@hi.is ; (2) Department of Pharmacy, University of Iceland; (3) Department of Odontology, University of Iceland.

Abstract
A gel has been developed containing a low dose of a matrix metalloproteinase inhibitor. MMP enzymes can be inhibited by low doses of doxycycline below levels likely to disrupt the oral flora. A clinical trial indicates that a mucoadhesive doxycycline gel has potential as a means of treating recurrent oral ulceration.

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Development of Mucoadhesive Sublingual Delivery System for Buprenorphine
Sudip K. Das and Nandita G. Das
Idaho State University, College of Pharmacy, Pocatello, ID 83209-8334, USA
das@pharmacy.isu.edu

Abstract
Mucoadhesive sublingual tablets were formulated using hydroxypropyl methyl cellulose. Formulations were evaluated for swelling and mucoadhesive properties, and for disintegration time using a novel flow-thru apparatus designed in our laboratory. With increase in polymer concentration, average matrix swelling values increased, disintegration time was prolonged and adhesive force was increased.

Abstract
This study describes the formulation, characterisation and preliminary clinical evaluation of mucoadhesive, semi-solid formulations containing hydroxyethylcellulose (HEC, 1-5%, w/w), polyvinylpyrrolidine (PVP, 2 or 3%, w/w), polycarbophil (PC, 1 or 3%, w/w) and tetracycline (5%, w/w, as the hydrochloride). Each formulation was characterised in terms of drug release, hardness, compressibility, adhesiveness (using a texture analyser in texture profile analysis mode), syringeability (using a texture analyser in compression mode) and adhesion to a mucin disc (measured as a detachment force using the texture analyser in tensile mode). The release exponent for the formulations ranged from 0.78+/-0.02 to 1.27+/-0.07, indicating that drug release was non-diffusion controlled. Increasing the concentrations of each polymeric component significantly increased the time required for 10 and 30% release of the original mass of tetracycline, due to both increased viscosity and, additionally, the unique swelling properties of the formulations. Increasing concentrations of each polymeric component also increased the hardness, compressibility, adhesiveness, syringeability and mucoadhesion of the formulations. The effects on product hardness, compressibility and syringeability may be due to increased product viscosity and, hence, increased resistance to compression. Similarly, the effects of these polymers on adhesiveness/mucoadhesion highlight their mucoadhesive nature and, importantly, the effects of polymer state (particularly PC) on these properties. Thus, in formulations where the neutralisation of PC was maximally suppressed, adhesiveness and mucoadhesion were also maximal. Interestingly, statistical interactions were primarily observed between the effects of HEC and PC on drug release, mechanical and mucoadhesive properties. These were explained by the effects of HEC on the physical state of PC, namely swollen or unswollen. In the preliminary clinical evaluation, a formulation was selected that offered an appropriate balance of the above physical properties and contained 3% HEC, 3% PVP and 1% PC, in addition to tetracycline 5% (as the hydrochloride). The clinical efficacy of this (test) formulation was compared to an identical tetracycline-devoid (control) formulation in nine periodontal pockets (=<5 mm depth). One week following administration of the test formulation, there was a significant improvement in periodontal health as identified by reduced numbers of sub-gingival microbial pathogens. Therefore, it can be concluded that, when used in combination with mechanical plaque removal, the tetracycline-containing semi-solid systems described in this study would augment such therapy by enhancing the removal of pathogens, thus improving periodontal health.

Abstract
In this study we used tensile strength measurements and a recently developed interpretation procedure to evaluate the mucoadhesive properties of a large set of gel preparations with diverse rheological properties. Multivariate data analysis in the form of principal component analysis (PCA) and partial least square projection to latent structures (PLS) was applied to extract useful information from the rather large quantities of data obtained. PCA showed that the selected series of gels was heterogeneous. Some groupings could be detected but none of the gels was identified as an outlier. By using PLS we investigated the relations between the rheological properties of a gel and the parameters defining the cohesiveness, as measured with the texture analyser used for the mucoadhesion measurements. The rheological properties proved to be important for the results of both the mucoadhesion and the cohesiveness measurements. Furthermore, by using PLS two different measurement configurations were evaluated and it was concluded that the combination of a relatively small volume of gel and two pieces of mucosa seems to be more appropriate than a large volume of gel in combination with one piece of mucosa.

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Influence of the Degree of Polymerization on the Behavior of Cellulose During Homogenization and Extrusion/Spheronization.
Kleinebudde P, Jumaa M, Saleh F.
AAPS PharmSci. 2000; 2 (3): article 21. DOI: 10.1208/ps020321
Influence of the Degree of Polymerization on the Behavior of Cellulose During Homogenization and Extrusion/Spheronization
Peter Kleinebudde,1 Muhannad Jumaa,2 and Firas El Saleh3

1Institute of Pharmaceutics & Biopharmaceutics, Martin-Luther-University, Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle, Germany;
2Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047
3Department of Pharmaceutics and Biopharmaceutics, Christian-Albrecht-University, Kiel, Germany

Correspondence to:
Peter Kleinebudde Tel: 49-345-552 51671 Fax: 49-345-5527029
Email: kleinebudde@pharmazie.uni-halle.de

Submitted: February 24, 2000; Accepted: June 30, 2000; Published: July 24, 2000

Keywords: Microcrystalline Cellulose, Degree of Polymerization, High-Pressure Homogenization, Extrusion/Spheronization, Gel and Sponge Model

Abstract
The study objective was to investigate the influence of the degree of polymerization (DP) of cellulose materials (microcrystalline cellulose [MCC] and powder cellulose [PC]) on the behavior of these materials during homogenization and extrusion/spheronization processes. Suspensions of the cellulose types with different DP values were homogenized using a high-pressure homogenizer. The particle size, agglomeration index, and apparent viscosity of these suspensions was determined at different times after pouring. Additionally, these different cellulose types were processed into pellets using the extrusion/spheronization method, and the water content and power consumption as a function of the DP were determined. Cellulose types with a high DP value showed greater particle size after homogenization than the types with a low DP value. In contrast, no relevant relationship between the apparent viscosity and DP could be observed. During the extrusion process, water content in the extrudate and pellet porosity were increased as the DP was increased for the extrudates produced at the same level of power consumption. MCC types with various DPs compared with PC provided a novel way of understanding the role of cellulose in the extrusion process. The DP showed a remarkable influence on the physicochemical properties of the cellulose materials and, consequently, on the behavior of these materials during the extrusion/spheronization process. It is postulated that the sponge model is more appropriate for the cellulose type with high DP (PC), whereas the gel model is more applicable to cellulose types with lower DP (MCC).

Abstract
Viscoelastic properties of granules may be studied using stress relaxation. The effect of viscoelastic properties of different lubricants, namely magnesium stearate (Mgst), talc and precirol, on granule compaction properties was examined using texture analyzer TA-XT2i^(R) at low pressure. Normalized compact curves of stress relaxation have been discussed in relation to some parameters (flowability, porosity, viscoelasticity as well as particle size). The literature shows that viscoelasticity is always present and it produces an accompanying plastic deformation.This study revealed that bonding in compacted granules lubricated with Mgst was higher than those in compacts lubricated with the other two lubricants being studied. When studying the partial porosity of granule beds, we see that this is the result of stored energy, like the tablet case and the problem of its capping. The small stress relaxation due to talc or precirol suggested that these materials deformed principally by energy storage. However, a qualitative characterization of Mgst as tablet lubricant would be that it avoids the accumulation of stress in the compact that causes the problem of capping due to the entrapped air and therefore facilitates the optimization of pharmaceutical manufacturing. It has been possible to normalize stress relaxation using the Wischert model, represented by the sum of several exponentials, according to the nature of the lubricant.The use of texture analyzer TA-XT2i^(R) was considered to be a good technique for the evaluation of the stress relaxation of solid particles in the compression process at low pressure. It permitted the observation that viscoelasticity is influenced by the lubricant used. The brittle fracture index, like Carr*s index values, has been correlated with the viscoelastic characteristics of granules.