Excipient polymeric excipients

The excipients used in solid dispersions can be broadly classified as (a) polymeric and (b) non-polymeric excipients. Polymeric excipients are the primary excipients, whereas the non-polymeric ones are the auxiliary excipients. Polymeric excipients are further classified based on their charge into the following categories (a) nonionic or non-pH-dependent and (b) ionic or pH-dependent polymers. Further, nonionic polymers are classified as polyvinyllactam polymers and cellulose ethers. The ionic polymers are further classified as cationic and anionic polymers (Fig. 4.2). 

Occasionally in the synthesis of the copolymers, insoluble material is produced. This results from polymer containing blocks of polyglycolide rather than the desired random structure. Obviously, such compositions would have considerable effect on the performance of controlled release formulations utilizing those polymers. This problem is particularly evident when one is seeking to utilize the 50 50 glycolide/lactide copolymer as a biodegradable excipient. However, with carefully controlled polymerization conditions, useful 50 50 polymer is readily produced. 

Occasionally, an unusual combination of polymeric excipient and bioactive agent can lead to unexpected biodegradation profiles. 

Strobel et al. (101) reported a unique approach to delivery of anticancer agents from lactide/glycolide polymers. The concept is based on the combination of misonidazole or adriamycin-releasing devices with radiation therapy or hyperthermia. Prototype devices consisted of orthodontic wire or sutures dip-coated with drug and polymeric excipient. The device was designed to be inserted through a catheter directly into a brain tumor. In vitro release studies showed the expected first-order release kinetics on the monolithic devices. 

The incompatibility of some macromolecules with lactide/glycolides has been observed. As with other polymeric excipients, lactide/glycolides will serve some but not all applications. 

JA Ranucci, IB Silverstein. Polymeric pharmaceutical excipients. In HA Lieberman, MM Rieger, GS Banker, eds. Pharmaceutical Dosage Forms Disperse Systems, Vol. 3, 2nd ed. New York Marcel Dekkter, 1998, pp 243-289. 

One of the most important advantages of HPLC over spectrophoto-metric methods lies in its specificity and selectivity due to its separation capability. Through chromatographic separations, the analytes of interest can be detected and quantified without interference from the typical matrix that includes excipients, antioxidants, preservatives, and dissolution media. Ion-pair HPLC was used to monitor the dissolution of pentamidine from EVA sustained-release film where polymeric matrices could create significant bias if a spectrophotometric method were used. Due to their strong UV absorbance, the antioxidants and preservatives (e.g., BHA, BHT, ascorbic acid and propyl gallate) are often the major... 

Peroxides are a very common impurity in many excipients, particularly polymeric excipients [56]. They are used as initiators in polymerisation reactions, but are difficult to remove. Ding [57] monitored the peroxide concentrations within polysorbate 80 solutions, and demonstrated the effect of light, heat and concentration on peroxide concentrations. The author showed that the peroxide concentrations increased 9-fold at the lowest polysorbate concentration versus increases of only 1.5-fold at the highest polysorbate concentration. However, the absolute peroxide levels at the higher concentration were much higher. 

BMS-204352, a novel substituted 3-fluorooxindole, is a potassium channel opener being developed for the treatment of stroke. Nassar et al. [96] reported on the development of a non-aqueous parenteral formulation of BMS-204352. This formulation was composed of a mixture of PEG 300, polysorbate 80, ethanol and water. The authors reported on the formation of 1-hydroxymethyl adduct of BMS-204352 (formaldehyde adduct), which was linked with residual levels of formaldehyde in the polymeric excipients. 

The drug may be incorporated in a slowly eroding matrix of waxy materials, embedded in a plastic matrix, complexed with anion exchange resins or incorporated in a water-insoluble hydrophilic matrix. Drug release from these systems occurs by several mechanisms diffusion, dissolution, ionic exchange or osmotic pressure [1,2], depending on the type of polymeric excipient present and the formulation used. 

The degradation rate can be controlled using acidic and basic excipients acidic excipients increase the degradation rates and facilitate a zero-order release rate over a 2-week period (Sparer et al. 1984). Basic additives increase the degradation time of the polymers and create a polymer that degrades specifically at the surface (Heller 1985). By careful choice of the excipient added, the degradation rate can be closely controlled. No experiments have shown the use of these polymers with proteins or peptides. This is not, however, indicative of the fact that these polymers are not compatible with proteins or peptides, but they are probably not the most appropriate polymeric carrier for oral delivery of biomacromolecules. 

Several examples will help to illustrate this point. For the manufacture of a polymeric excipient, full GMPs are applied at the polymerization step because there is usually no significant purification after the polymer is formed. For a small molecule excipient such as a solvent or alcohol, full GMP principles must be applied no later than the start of purification, which is usually a distillation step. Finally for a salt or inorganic powder, full GMPs are applied at the formation of the salt or its purification step such as crystallization. 

Zhang, H., and Ray, K. (2007). Profiling impurities in a taxol formulation Application of a mass-dependent mass defect filter to remove polymeric excipient interferences. In Proceedings of the 55th ASMS Conference on Mass Spectrometry and Allied Topics, Indianapolis, IN. 

The primary coating materials, usually polymeric (film formers), often require the addition of other excipients such as plasticizers, pore formers, colorants, or antiaggregation agents for the coating to perform in the desired fashion or for the product to be manufactured conveniently.2 These components have been the subject of numerous studies and reviews.31,32 The components that affect/modify the release from these systems are film formers, plasticizers, and pore formers and are discussed below. 

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