Polymers Controlling Drug Release

A great and valuable achievement of pharmaceutical technology in the 20th century was the development of controlled-release therapeutic systems. 

1 Polymer Solvents, Micelle-forming Agents and Dendrimers 

The majority of active substances used currently are not very water-soluble. A very important technological task is to enhance water solubility. Three possibilities concerning polymers are going to be presented i) formulation of polymer dispersions and polymer solutions, ii) incorporation of apolar active substances into the micelles formed from copolymers, and iii) encapsulation of the active substance in dendrimers or its binding to the functional groups of the dendrimer [7, 9]. 

It was Sekiguchi and Obi [25] who developed solid solutions. The active substance which is insoluble or poorly soluble in water substitutes the solvent 

Place of application vascular system (infusion) subcutis (implantation skin (transdermal) ocular systems uterin systems  

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Key words biodegradable polymers controlled drug release mathematical... 

Heller, J., Controlled drug release from poly(ortho esters) A surface eroding polymer, J. Control. Rel., 2, 167-177, 1985. 

Noteable are recent studies on the generation of polymer particles as carriers for controlled drug release [333] and of cationic solid lipid micro-particles as synthetic carriers for the targeted delivery of macromolecules to phagocytic antigen-presenting cells [334]. The industrial interest, although rarely disclosed, is evident from the patents filed in the field (see, e.g., [335, 336]). 

Controlled drug delivery, membrane technology in, 15 847-848 Controlled drug release formulations (CDRFs), 9 51, 55 polymers in, 9 71-73 Controlled drug release systems, 9 50-51 design, 9 51-52 development, 9 55-57 intelligent, 9 56-57 in market, 9 83—85... 

With continuous development of systems for controlled drug release, new materials are being used whose influence on peptide stability must be carefully examined. Thus, the model hexapeptide Val-Tyr-Pro-Asn-Gly-Ala (Fig. 6.30) embedded in poly (vinyl alcohol) and poly(vinyl pyrrolidone) matrices had rates of deamidation that increased with increasing water content or water activity, and, hence, with decreasing glass transition temperature (Tg). However, the degradation behavior in the two polymers differed so that chemical reactivity could not be predicted from water content, water activity, or T% alone. Furthermore, the hexapeptide was less stable in such hydrated polymeric matrices than in aqueous buffer or lyophilized polymer-free powders [132],... 

For an erosion-induced drug delivery system compactable cellulose ethers are suitable polymers [103]. Drug release, which is controlled by the erosion/dissolution of these polymeric layers, may be pH-dependent if an acid or basic polymer is used. 

Muscles contract and expand in response to electrical, thermal, and chemical stimuli. Certain polymers, such as synthetic polypeptides, are known to change shape on application of electric current, temperature, and chemical environment. For instance, selected bioelastic smart materials expand in salt solutions and may be used in desalination efforts and as salt concentration sensors. Polypeptides and other polymeric materials are being studied in tissue reconstruction, as adhesive barriers to prevent adhesion growth between surgically operated tissues, and in controlled drug release, where the material is designed to behave in a predetermined matter according to a specific chemical environment. 

This book is a companion volume to Pharmaceutical Technology Controlled Drug Release, Volume 1, edited by M.H.Rubinstein and published in 1987. It focused on the different types of polymeric materials used in controlled release. This book extends these concepts to include drug properties, design and optimization, coating, the effect of food and pharmacokinetics. It also reflects the growing interest in biodegradable polymers in oral and topical formulations and the use of sterile implants. 

Alkyl monoesters of poly(vinyl methyl ether-maleic anhydride) (PVM-MA) are bioerodible acidic polymers that are used to control drug release. In biological fluids with poor buffering capacity, drug release from the polymers and their dissolution are slowed owing to the lower pH on the polymer surface. We studied whether the release of timolol from matrices of monoisopropyl ester of PVM-MA in vitro and in vivo in rabbits eyes could be affected by disodium phosphate in the matrices. Addition of disodium phosphate to the matrices doubled the release rate of timolol in vitro, but it did not affect the bulk pH of the dissolution medium. On the basis of the timolol concentrations in the tear fluid and in systemic circulation, disodium phosphate seems to accelerate drug release in vivo also. Disodium phosphate probably affects the rate of dmg release by increasing the microenvironmental pH on the polymer surface. 

Bioerodible alkyl monoesters of poly(vinyl methyl ether-maleic anhydride) (PVM-MA) (Fig. 1) can be used to control drug release. Being acidic, ionizable polymers the pH of the disolution medium affects the rate of polymer dissolution [1]. 

During polymer dissolution, the pH on the polymer surface decreases. This decreases the rate of polymer dissolution. When buffer is added to dissolution medium, hydrogen ions are neutralized by the buffer on the surface of the polymer. The buffer concentration thus affects the rates of polymer dissolution and erosion-controlled drug release [1]. In biological fluids with poor... 

Phase transition in gels in response to biochemical reactions [27,28]. Polymer gels were synthesized in which an enzyme (urease) or a biologically active protein (lectin) was immobilized. The volume phase transitions were observed in such gels when biochemical reactions took place. Such mechano-biochemical gels will be used in devices such as, sensors, selective absorbers, and biochemically controlled drug release. 

Langoth et al. [86] studied the properties of matrix-based tablets containing the novel pentapeptide leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) that has been shown to have pain-modulating properties. The matrix-based tablets were made with the thiolated polymer PCP. The covalent attachment of cysteine to the anionic polymer PCP leads to an improvement of the stability of matrix tablets, enhances the mucoadhesive properties, and increases the inhibitory potency of PCP towards buccal enzymes. All these factors lead to stability of the peptide and a controlled drug release for the peptide was obtained for more than 24 h. Also, the tablets based on thiolated PCP remained attached on freshly excised porcine mucosa 1.8 times longer than the corresponding unmodified polymer. 

Heller, J., Baker, R. W., et al. Controlled drug release by polymer dissolution. I. Partial esters of maleic anhydride copolymers—Properties and theory. J. Appl. Polym. Sci. 22 1991-2009, 1978. 

Heller, J., and Trescony, P. Controlled drug release by polymer dissolution 11. Enzyme-mediated delivery device. J. Pharm. Sci. 68 919—921, 1979. 

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