Production, Characterization and Application of Multiple Modified Maize Starches in the Formulation of Oral Solid Dosage Forms of Gentamicin Sulphate

Abstract

Modified and unmodified starches in current use have limited applications in pharmaceutical industries. Extending the modification beyond the existing level may increase their applicability in dosage forms design especially for gentamicin sulphate, a difficult to formulate broad spectrum antibiotic for oral administration. In this research, maize starch was chemically modified to three levels (primary, secondary and tertiary) using pre-determined optimal conditions and established modification techniques (oxidation, substitution/complexation and cross-linking). Oxidation of maize starch was carried out with hydrogen peroxide (H) and sodium hypochlorite (N), substitution/complexation was carried out using citric acid (C), while cross-linking was carried out with glutaraldehyde (G). Products arising from the first level (primary) modification were subjected to second level (secondary) modification such that starches treated with H were further modified with N or C or G. Those treated with N were modified with C or G. Finally the secondary modified starches that did not contain G were treated with G in the third level (tertiary) modification. Modification was confirmed by X-ray diffraction studies and differential scanning calorimetry (DSC). The modified starches were evaluated by assessing some of their physical and micromeritic properties. Thereafter, some of the modified products were used to formulate gentamicin sulphate capsules for oral administration. The capsules were thereafter evaluated using British Pharmacopoeia specifications. Biopharmaceutical evaluation of the gentamicin sulphate and the formulations were also carried out using sensitive organisms: E. coli, S. typhi, K. pneumonia and S. aureus. The results of the study were analysed statistically using analysis of variance with significance set at p < 0.05. Preliminary studies show that the best condition for the modification of maize starch was heating in a water bath at a temperature of 70 oC for 30 min using the appropriate modification agent. There were marked differences in the X-ray diffraction patterns of unmodified and modified starches. The DSC thermographs of the modified starches differ from one another. Among the modified starches, H-, C-, HN- and HC-modified starches have good flow properties indicated by their angles of repose and Carr’s indices, while the flow of G-, CG- and HCG-modified starches can be described as passable. The N-, HG-, NC-, NG-, HNGand NCG-modified starches exhibited very poor flow. The HNG- and HN-modified starches exhibited highest swelling in aqueous system, while the N-modified starch showed negative swelling. The N-modified starches swelling behaviour was similar to that of Ac-di-sol®. Biopharmaceutical evaluation indicated that gentamicin sulphate at 500 mg/kg and above, could permeate into systemic circulation with plasma concentrations achieved inhibiting the growth of Staphylococcus aureus, while at concentrations below 500 mg/kg could not permeate into systemic circulation. Gentamicin sulphate at 1000-, 750- and 500- mg/70 kg corresponding to 14.28-, 10.71- and 7.14- mg/kg respectively were able to maintain concentrations that inhibited the growth of the sensitive bacteria in the GIT. Gentamicin sulphate (250 mg) granules formulated with the Nmodified starch as diluents were quick drying because the granules were not hygroscopic. The formulated gentamicin sulphate capsules released most of the content within 2 min of dissolution study.