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A demonstration that, in the polymerization of divinyl monomers, the double bond included in the cyclodextrins (CD) cavity does not react with the growing radical chain is presented. This results in soluble, linear polymers containing pendant vinyl unsaturations.

Cefuroxime axetil (CA) has exhibited interactions with the polymers hydroxypropyl methylcellulose phthalate, cellulose acetate trimellitate, and Eudragit E resulting in the generation of unacceptable amounts of impurities and degradation. Formulations, which mask the bitter taste of CA and release it immediately in the stomach, have therefore not been possible. In an attempt to overcome the interaction with CA, we report a self-associated cationic polymer (NREP) containing methyl methacrylate (MMA), 2-hydroxy ethylmethacrylate (HEMA), and 4-vinyl pyridine (4-VP). The hydrogen bonding between the pyridine nitrogen and the hydroxyl groups of HEMA results in strong intrachain associations, prevents interactions between NREP and CA, and inhibits degradation of CA. This has been validated by differential scanning calorimetry, Fourier transform infrared spectroscopy, NMR, and high-performance liquid chromatography analysis. These self-associations restrict polymer chain motions, enhance biocompatibility, and lead to a higher Tg, which ensures that NREP does not become tacky in processes involving heat. The judicious choice of the hydrophobic and hydrophilic monomers renders the polymer hydrophobic enough as to mask the bitter taste of CA at near neutral pH. Incorporation of the basic monomer 4-VP ensures rapid dissolution of the polymer and release of CA at the acidic pH prevalent in the stomach. The work indicates an approach to design pH-sensitive polymers for dosage forms that meet the pharmacokinetic requirements of the drug.

Blends of conventional reverse enteric polymer with enteric polymers result in insoluble polyelectrolyte complexes and hence cannot be used in film coatings. We report a new set of miscible blends of a new reverse enteric polymer (NREP) synthesized by us with enteric and pH-independent polymers. The nature of interactions between polymers in the blends has been established by analyzing Fourier transform infrared (FTIR) spectra. The extent of interaction has been investigated by thermal analysis and quantified in terms of parameters K1 and K2 in the Schneider equation. Based on these values, the interactions between NREP and these polymers have been ranked in the order EC (ethylcellulose) < ES (Eudragit S) < HPMCP (hydroxypropyl methylcellulose phthalate). The quantification of interactions in blends helps explain the release pattern of cefuroxime axetil (CA) at gastric pH and tailor the release of other drugs according to their pharmacokinetic characteristics. The understanding also provides a more rational approach for selection of polymers and their content in the coating compositions, rather than an empirical approach.