Formulation and evaluation of propylene glycol monostearate microspheres for sustained release of nitrofurantoin

Sustained release of nitrofurantoin (NFT) from microspheres of propylene glycol monostearate (PGM) and of PGM and ethoxylated stearyl alcohol (ESA) prepared by the meltable dispersion and cooling process was investigated. The microspheres (30-850 mu) were nonsticky, discrete and free flowing. Both the rate and extent of in vitro release of NFT (from NFT-PGM microspheres in distilled water at 37 degrees C under constant agitation at 50 rpm) declined with decreasing NFT/PGM ratio. The effect of incorporating ESA over the range of 0.01 to 0.05% w/w of PGM in formulations with NFT/PGM ratios of 1:1, 1:1.5 and 1:4, studied under similar experimental conditions revealed that NFT release was maximum in the range of 0.02 to 0.035% ESA. The effect of pH on NFT release from microspheres with 0.03% ESA and without ESA at NFT/PGM ratios of 1:1 and 1:4, was investigated in buffer solutions at pH values of 1.2, 5.8 and 7.2. The pH-dependent solubility and dissolution of NFT and PGM, in addition to NFT/PGM ratio, were found to control the rate and extent of NFT release. Both scanning electron photomicrography and contact angle measurements suggested that about 0.03% ESA was critical for the formulations studied. The in vitro evaluation of adhesion of various polymers to rabbit stomach tissue was investigated. The polymers, CLD, ACDISOL, polycarbophil and calcium polycarbophil were investigated for potential use as bioadhesives. The modified balance method developed and used to evaluate the polymers adhesion to rabbit stomach tissue in vitro at different pH levels was reproducible and could detect change in adhesive force as little as 10 mg weight. Maximum adhesion for polymers CLD and polycarbophil was observed at pH 5.8, while that of ACDISOL was at pH 7.2. The polymer, calcium polycarbophil, showed essentially no adhesion at all. The results revealed that CLD was superior and ACDISOL was inferior to polycarbophil under all three pH conditions investigated. In vitro release studies of the drug from microspheres mixed in various proportions with bioadhesive polymer CLD in phosphate buffer at pH 5.8 indicated that the presence of the polymer did not significantly hinder the drug release. (Abstract shortened with permission of author.