Pierre Buri

Mechanisms of solute release from porous hydrophilic polymers

Abstract Porous hydrophilic discs were prepared from two grades of poly(vinyl alcohol) of varying degree of hydrolysis. The influence of the molecular size of the tracer used (potassium chloride, phenylpropanolamine hydrochloride and bovine serum albumin), that of the addition of a second water-soluble polymer poly(N-vinyl-2-pyrrolidone) and poly(ethylene glycol)) and the effect of the tracer/excipient ratio on the release profile were examined. Finally the role of the dynamic swelling and the dissolution of the polymer matrix on the release mechanism are discussed.

Chitosan: A Unique Polysaccharide for Drug Delivery

The aim of this review is to give an insight into the many potential applications of chitosan as a pharmaceutical drug carrier. The first part of this review concerns the principal uses of chitosan as an excipient in oral formulations (particularly as a direct tableting agent) and as a vehicle for parenteral drug delivery devices. The use of chitosan to manufacture sustained-release systems deliverable by other routes (nasal, ophthalmic, transdermal, and implantable devices) is discussed in the second part.

Surface, interfacial and molecular aspects of polymer bioadhesion on soft tissues

Abstract Interfacial phenomena related to the adhesive properties of synthetic polymers, hydrocolloids and related systems in contact with soft, natural tissues are discussed. The nature of the adhesive interface, the surface roughness, the chemical structure of the bioadhesive-candidate material, the swelling (hydration) at the adhesive interface, and the dynamic development of the bioadhesive bond strength are analyzed in terms of molecular and surface theories. Available in vitro testing techniques for bioadhesion provide an indication of the efficiency of proposed polymers as bioadhesives. These theoretical analyses and experimental results are used to establish general guidelines for the development of bioadhesive controlled release systems of bioactive agents for buccal, nasal, gastric, intestinal, urinary and rectal uses.

Topical use of chitosan in ophthalmology : tolerance assessment and evaluation of precorneal retention

The mucoadhesive polysaccharide chitosan was evaluated as a potential component in ophthalmic gels for enabling increased precorneal drug residence times. This cationic vehicle was expected to slow down drug elimination by the lacrymal flow both by increasing solution viscosity and by interacting with the negative charges of the mucus. The molecular weight (Mw) and concentration of polysaccharide were studied in four types of chitosan as parameters that might influence ocular tolerability and precorneal residence time of formulations containing tobramycin as therapeutic agent. An ocular irritation test, using confocal laser scanning ophthalmoscopy (CLSO) combined with corneal fluorescein staining, clearly demonstrated the excellent tolerance of chitosan after topical administration onto the corneal surface. Gamma scintigraphic data showed that the clearance of the formulations labelled with 99mTc-DTPA was significantly delayed in the presence of chitosan with respect to the commercial collyrium (Tobrex(R)), regardless of the concentration and of the molecular weight of chitosan in solution. At least a 3-fold increase of the corneal residence time was achieved in the presence of chitosan when compared to Tobrex(R).

Drug absorption sites in the gastrointestinal tract and dosage forms for site-specific delivery

The authors firstly review the literature dealing with drug absorption sites in the gastrointestinal tract. Descriptions are given of the methods used in determining the location of these sites, and the advantages and disavantages of each method are critically discussed. The results obtained concerning the absorption sites of the drugs used in the in vivo methods studied are given in a tabular form and several factors influencing drug absorption are briefly reported. Mechanisms of drug absorption in the human body and their influence on absorption sites are examined. Finally, there is a discussion of various dosage forms which are used for targetting drug absorption to specific sites.

A novel in situ method to test polymers and coated microparticles for bioadhesion

A simple, quantitative and realistic in situ method to test the bioadhesive potential of polymers was developed. In this technique, the glass spheres or drug crystals were first coated with the polymers to be tested. Later, known amounts of these coated particles were placed on rat jejunum or stomach and kept in a humid environment. The tissue was then washed with phosphate buffer (for jejunum) or dilute HCl (for stomach) at a constant rate. The percent of particles retained on the tissue was considered as an index of bioadhesion. Among the polymers tested, polycarbophil and sodium carboxymethylcellulose-coated particles adhered stronger to the mucus than those with hydroxypropylmethylcellulose, methylcellulose and pectin. All the particles adhered better to the stomach than to the intestine.

Modelling of drug diffusion through swellable polymeric systems

Abstract A drug diffusion model for the case of diffusion of an initially uniformly distributed drug through a polymeric matrix is presented and solved. Drug diffusion from a single surface is analyzed for the case of countercurrent diffusion of a solvent which is thermodynamically compatible with the polymer. Due to swelling, considerable volume expansion is observed leading to a moving-boundary diffusion problem. Drug concentration profiles within the polymer and drug release rates can be determined. The results are in agreement with experimental data obtained for the system of KCl distributed in hydrophilic hydroxypropyl methyl cellulose matrices, in the form of tablets.

Factors and strategies for improving buccal absorption of peptides

Peptides and polypeptides have important pharmacological properties but only a limited number (e.g. insulin, oxytocin, vasopressin) have been exploited as therapeutics because of problems related to their delivery. The buccal mucosa offers an alternative route to conventional, parenteral administration. Peptides are generally not well absorbed through mucosae because of their molecular size, hydrophilicity and the low permeability of the membrane. Peptide transport across buccal mucosa occurs via passive diffusion and is often accompanied by varying degrees of metabolism. This review describes various approaches to improve the buccal absorption of peptides including the use of penetration enhancers to increase membrane permeability and/or the addition of enzyme inhibitors to increase their stability. Other strategies including molecular modification with bioreversible chemical groups or specific formulations such as bioadhesive delivery systems are also discussed.

Monoolein: a review of the pharmaceutical applications

Although monoolein is a well-known molecule commonly used as an emulsifying agent and as a food additive since the 1950s, its potential applicability in the pharmaceutical industry has not been considered in great detail. Recently, there has been a flurry of activity concerned with the possibility of using monoolein as a material for different pharmaceutical applications. The explosion of interest in this field is evidenced by an increase in the number of publications in the area (1). Figure 1 shows the percentage of consulted references of monoolein versus publication year. It is important to point out that only articles falling in the pharmaceutical area were considered when creating this graphic. Between 1978 and 1987, monoolein was used mainly as an absorption enhancer in combination with bile salts and as an emulsifier. It was in 1984 that monoolein was first

Cellulose Matrices for Zero-Order Release of Soluble Drugs

AbstractRelease of two very soluble beta adrenergic blockers namely: metoprolol tartrate and alprenolol HCl from cellulose matrices containing hydroxypropylcellulose (HPC) or sodium carboxymethylcellulose (Na CMC) or methylcellulose (MC), or MC + Na CMC or HPC + Na CMC in different ratios was studied in distilled water using USP dissolution apparatus 2. Increase in the ratio of total polymer to drug has decreased the release rate in a nonlinear manner. When only one polymer (HPC or Na CMC) was used, the release profiles were of first-order or sigmoidal in nature respectively. MC matrices disintegrated in < 1 h. By mixing the drug with an optimum amount of the nonionic (HPC or MC) and anionic (Na CMC) polymers, zero-order release profiles with excellent reproducibility were obtained. Rate of erosion of the matrix was 2.5 times higher when drug, Na CMC and HPC were present compared to the matrix containing only drug and HPC. This indicates that the diffusional pathlength for the drug increases with time whe...