Hydrocortisone release, polymer

Figure 4, Rate of polymer dissolution and hydrocortisone release from n-butyl half-ester of methyl vinyl ether-maleic anhydride copolymer containing 10 wt% drug, (Reprinted with permission from Ref. 12. Copyright 1980, John Wiley ...

Nair and Chien [44] compared patches and tablets of different polymers (sodium carboxymethylcellulose, carbopol, polyethylene oxide, polymethyl vinyl ether-maleic anhydride, tragacanth) regarding their release characteristics of four drugs (chlorheximide, clotrimazole, benzocaine, and hydrocortisone). They observed sus-... 

Kwon and coworkers described solid polyelectrolyte complex systems which dissolve rapidly in response to small electric currents. The solid doses were based on poly(ethyl oxazoline) and poly(methacrylic acid) with a repeating unit stoichiometry of 1 1. Insulin was released in response to slight electric currents due to electrically induced polymer dissolution [380]. In similar work Kwon and coworkers [381] studied release of edrophonium chloride and hydrocortisone from poly(2-acrylamido-2-methylpropane sulfonate-co-n-butyl methacrylate). An on/oflf mechanism of the edrophonium chloride release was observed and was attributed to ion exchange of solute and hydroxonium ion. The cationic solute release was assisted by electrostatic forces, whereas release of the neutral hydrocortisone solute was only affected by swelling and deswelling. 

Figure 2 shows the results obtained when this polymer, containing dispersed hydrocortisone, is surrounded by a hydrogel containing immobilized urease and release of hydrocortisone is studied as a function of external urea concentration (2). Although this system has very little therapeutic relevance, it did establish the feasibility of this concept and served as the basis for the development of a more useful system. 

Fig. 26 Cross-sectional view of a bioerosion-regulated hydrocortisone delivery system, a feedback-regulated drug delivery system, showing the drug-dispersed monolithic bioerodible polymer matrix with surface-immobilized ureases. The mechanism of release and time course for the urea-activated release of hydrocortisone are also shown. (From Ref > 1)...

Many other polymers have been tested as backbonesfor prodrugs. As examples, one may list poly-L-(glutamic acid) for clonidine controlled release (52), hyaluronic acid for hydrocortisone and derivatives (53-55), or the synthetic polyanionic polymer pyran for the antitumor, antibacterial, and antiviral agent muramyl dipeptide (56). Hyaluronic acid and pyran are interesting in the sense that they add a new dimension to the macromolecular prodrug approach. Hyaluronic acid is believed to be potentially useful for the control of infec-... 

When a water-insoluble drug such as hydrocortisone is physically dispersed in the polymer and the polymer fabricated into thin disks which are then placed in a buffer at pH 7.4, release kinetics shown in Fig. 1 are obtained. Clearly, this system exhibits excellent zero order drug release kinetics with concomitant linear rate of polymer weight loss. The simultaneous polymer erosion and drug release is a clear indication that erosion occurs at the surface of the device and that drug release is controlled by erosion of the polymer. 

Release of hydrocortisone. Initial exploratory in vitro studies designed to ascertain the usefulness of this polymer system have been carried out with a polymer based on 1,2,6-hexanetriol and various alkyl ortho esters. In these studies 2 wt% hydrocortisone was physically mixed into the ointment and the mixture placed into an erosion cell. A pH 7.4 buffer solution was then pumped across the cell at 9.5 ml/h, samples collected using an automatic fraction collector and analyzed for hydrocortisone by HPLC. The same study was also carried out by mixing into the ointment 2 wt% hydrocortisone and 2 wt% adipic acid. Results of these studies are shown in Fig. 32 [49]. The data clearly shows that without the incorporation of an acidic excipient erosion rate of the polymer is so slow that no hydrocortisone is released for two days. However, when an acidic excipient is mixed into the polymer, a fairly constant release is obtained. 

Fig. 32. Release of hydrocortisone from a polymer prepared from 1,2,6-hexanetriol and triethyl-...

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