Drug absorption may be enhanced for certain tablet dosage forms by increasing the stomach transit time or by retaining the dosage form in the stomach for longer time. Even though gastric retentive drug delivery could be achieved by different mechanisms, the floating tablet offers a simple and practical approach to achieve increased gastric residence time. The delivery system was designed such that, it was capable of floating in gastric fluid for longer than usual period of time and thereby assisted in sustaining the rate of delivery of drugs and thereby improved the maximum absorption in the upper part of the gastrointestinal tract. The drugs that were mostly absorbed from the upper part of the intestinal tract might have an absorption window in the acidic pH range but the involuntary peristaltic movement empties out the dosage form from the stomach within a short period of time. In such cases, a gastric retentive delivery system would be adequate and would ensure longer gastric residence time. As such a gastric retentive delivery system combined with sustained release property was designed in this research work. The sustained release dosages developed contain a polymer that controlled the rate of drug release. The physical and chemical characteristics of drug release controlling agent directly influenced the rate of drug released. The study utilized natural hydrophilic polymers with different viscosities. The purpose of this study was to investigate the effect of viscosity of hydrophilic polymer on the gastric retentive drug delivery system of Gabapentin sustained release tablets to determine how it affected the ability of the tablet to float in simulated gastric fluid. The effect of viscosity of hydrophilic polymer on the in-vitro rate of drug release, compressibility and physical tablet properties were also studied.
The experimental results were analyzed using descriptive, bivariate and multivariate statistical tools. It was found that the rate of drug release from gastric retentive Gabapentin 300 mg sustained release tablets was increased with time in all experimental conditions evaluated. However, based on multivariate statistical analysis, it was observed that as the viscosity of Hypromellose, USP increased, the rate of drug release was significantly decreased (p<0.0001) irrespective of polymer concentration. It was observed that the correlation coefficient (R²) for the rate of drug release from tablets formulated using 5%, 15% and 25% w/w of hydrophilic polymer concentration 0.77, 0.81 and 0.84 respectively. Based on the multivariate statistical data analysis, it was observed that the fraction of tablets that remained floated in simulated gastric fluid was significantly decreased (p<0.0001) with time irrespective of polymer concentration. However as the viscosity of Hypromellose, USP increased, the fraction of tablets remain floated was significantly increased (p<0.0001) which was evident in tablets formulated with 5% (R² = 0.92), 15% (R² = 0.94) and 25% (R² = 0.91) % w/w of Hypromellose USP. Effect of viscosity of Hypromellose, USP at 5, 15 and 25% w/w on the tablet floatation lag time was also evaluated. It was observed that the tablet floatation lag time was significantly decreased with increased viscosity and concentration of Hypromellose, USP at 5% (R² = 0.97, p=0.0004), 15 (R² = 0.94, p=0.0013) and 25 (R² = 0.96, p=0.0006) % w/w in the formulation.
Tablet physical properties were also analyzed to evaluate the effect of viscosity and concentration of Hypromellose, USP on the tabletting process attributes as well as the quality attributes of the tablets. Tablet compressibility was influenced by the viscosity of hydrophilic polymer. As the viscosity of Hypromellose, USP increased from 100 to 100000 cps the compressibility index calculated as Carr’s Index and Hausner ratio was also increased from 26 to 42 and from 1.34 to 1.72 respectively. Tablet weight variation was unaffected by the viscosity (p = 0.56) and concentration (p = 0.23) of the polymer and also the applied compression force (p = 0.44). Tablet hardness was significantly increased (p<0.0001, R² = 0.94) with increased polymer viscosity, concentration and compression force. Tablet thickness was significantly decreased (p<0.0001, R² = 0.88) with increased polymer viscosity (p<0.0001) and compression force (p<0.0001). However, tablet thickness was unaffected by the polymer concentration (p = 0.09). Tablet friability was unaffected with polymer viscosity (p = 0.33) and concentration (p = 0.86). However, tablet friability was significantly decreased with increased compression force (p<0.0001). In summary, the study concluded that the viscosity of hydrophilic polymer directly influenced the rate of drug release for the dosage form developed. Viscosity of hydrophilic polymer also influenced the floatation ability of Gabapentin tablets. In addition, the viscosity of hydrophilic polymer was shown to yield direct effect on the physical properties of the delivery system developed.