Excipients polymers

Okhamafe, A.O. York, P. Thermal characterization of drug/polymer and excipient/polymer interactions in some film coating formulations. J. Pharm. Pharmacol. 1989, 41, 1-6. 

Eudragit E PO excipient, polymer powds Wacker HDK H15 excipient, polysulfide... 

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. 

Phase separation microencapsulation procedures are suitable for entrapping water-soluble agents in lactide/glycolide excipients. Generally, the phase separation process involves coacervation of the polymer from an organic solvent by addition of a nonsolvent such as silicone oil. This process has proven useful for microencapsulation of water-soluble peptides and macromolecules (48). 

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. 

One useful drug delivery system is derived from polymers that contain acid-labile linkages in their backbones because hydrolysis rates of such polymers can be readily manipulated by means of acidic or basic excipients physically incorporated into the matrix (2). Further, under certain conditions the hydrolysis of such polymers can be... 

When a hydrophobic polymer with a physically dispersed acidic excipient is placed into an aqueous environment, water will diffuse into the polymer, dissolving the acidic excipient, and consequently the lowered pH will accelerate hydrolysis of the ortho ester bonds. The process is shown schematically in Fig. 6 (18). It is clear that the erosional behavior of the device will be determined by the relative movements of the hydration front Vj and that of the erosion front V2- If Vj > V2, the thickness of the reaction zone will gradually increase and at some point the matrix will be completely permeated with water, thus leading to an eventual bulk erosion process. On the other hand, if V2 = Vj, a surface erosion process wiU take place, and the rate of polymer erosion will be completely determined by the rate at which water intrudes into the matrix. 

Convincing evidence for a surface erosion process is shown in Fig. 8, which shows the concomitant release of the incorporated marker, methylene blue, release of the anhydride excipient hydrolysis product, succinic acid, and total weight loss of the device. According to these data, the release of an incorporated drug from an anhydride-catalyzed erosion of poly (ortho esters) can be unambiguously described by a polymer surface erosion mechanism. 

A plausible mechanism for the erosion of devices that contain Mg(OH)2 is shown in Fig. 14 (2). According to this mechanism, the base stabilizes the interior of the device and erosion can only occur in the surface layers where the base has been eluted or neutralized. This is believed to occur by water intrusion into the matrix and diffusion of the slightly water-soluble basic excipient out of the device where it is neutralized by the external buffer. Polymer erosion then occurs in the base-depleted layer. 

Initial work with poly (ortho esters) focused on norethindrone and the use of water-soluble excipients such as Na2C03, NaCl, and Na2S04 (27). As described by Fedors (28), the inclusion of such water-soluble salts leads to an osmotically driven water intake into the polymer. This water intake leads to polymer swelling with consequent release of the incorporated norethindrone. The effect of incorporated NaCl and Na2C03 on erosion rate as compared to the... 

Because swelling and consequent bulk erosion induced by the water-soluble salt is not desirable, use of the low-water-solubility, sUghtly acidic salt calcium lactate was investigated (30). By using this excipient it was hoped that a lowering of the pH within the surface layers of the device would take place and release of the drug would be controlled by polymer erosion confined to the surface layers of the device. In these experiments norethindrone was replaced by the currently favored steroid levonorgestrel. 

Because acid excipients can be used to achieve rapid polymer erosion, the possibility of preparing devices useful for oral delivery was investigated (31). In one such system, 2 wt% phthalic anhydride was incorporated into a polymer prepared from the diketene acetal, trans-cyclohexanedimethanol and C-labeled 1,6-hexanediol and polymer erosion followed in a pH 7 buffer and in pH 1.5 canine... 

When acidic or latent acidic excipients (anhydrides) are incorporated into the polymer to control erosion rate, the polymers become quite sensitive to moisture and heat and must be processed in a dry environment. A rigorous exclusion of moisture is particularly important with materials that are designed to erode in less than 24 hr. Such materials may contain up to 5 wt% of an acidic catalyst and are analogous to a "loaded gun" in that even the slightest amount of moisture will initiate hydrolysis at the elevated processing temperatures. ... 

Heller, J., Control of polymer surface erosion by the use of excipients, in Polymers in Medicine II (E. ChieUni, P. C. Migliaresi, Giusti, and L. Nicolais, eds.). Plenum Press, New York, 1986, pp. 357-368. 

With transdermal dosage forms being of great importance of late, it is advisable to test for compatibilities with ointment excipients and with polymers (e.g., ethylvinyl polymer, if that is the desired barrier). 

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