Gellan gum based gastroretentive tablets for bioavailability enhancement of cilnidipine in human volunteers.

Cilnidipine, a fourth-generation both L-and N-type calcium channel blocker (CCB) is safe and effective in lowering blood-pressure without reflex tachycardia compared to other dihydropyridine CCBs. However, its low solubility coupled with extensive first-pass metabolism results in very low oral bioavailability. Thus the study aimed to improve oral bioavailability of Cilnidipine by increasing its gastrointestinal transit-time and mucoadhesion. Gastroretentive tablets were prepared by direct-compression technique using gellan gum as hydrogel forming polymer and sodium bicarbonate as gas-generating agent. Statistical optimization was carried out by design approach which showed that gellan gum has significant impact on floating lag time, mucoadhesive strength, % drug release at 1 h and time to release 90% of drug. Drug release study revealed that optimized tablets prolonged drug release for 12 h and followed anomalous-diffusion indicating drug release is by coupling of both diffusion and erosion mechanism. Intragastric behaviour of formulation in human volunteers revealed that radio-opaque tablets remain buoyant in stomach for more than 6 h with sufficient mucoadhesion. Comparative pharmacokinetic profiling in human subjects revealed that relative bioavailability of Cilnidipine GR tablets was enhanced compared to reference tablets. Thus concluded that gastroretentive tablets to be promising strategy for improved oral bioavailability of Cilnidipine for effective treatment of hypertension.

Formulation, Optimization, and In vivo Evaluation of Gastroretentive Drug Delivery System of Nifedipine for the Treatment of Preeclampsia.

The study aimed to develop gastroretentive drug delivery system of nifedipine, its optimization, and in vivo evaluation. Bilayered tablet of nifedipine was prepared using central composite design with 3 factors, 5 responses, and 15 experimental trials. Response surface methodology along with numerical and graphical optimization was used to select the best formulation. Scanning electron microscopy study of optimized tablet at different time interval was carried out which showed formation of porous structure on the tablet surface. In vivo studies for optimized formulation were carried out on 10 healthy human volunteers and obtained pharmacokinetic parameters were compared with the marketed formulation, "Nicardia XL." Optimized formulation containing 3.083 mg HPMC K15M, 29.859 mg HPMC E15LV, and 3.541 mg Carbopol 974P releases the drug in a desired manner and remain buoyant for more than 12 h in human stomach. Both the formulations were found to have similar in vitro release profile (f1 4.5089 and f2 55.8274) and also were found to be bioequivalent. Finally, the stability study of the optimized formulation proved the integrity of the optimized formulation. Hence, the data suggest gastroretention as a promising approach to enhance bioavailability of nifedipine.

Zeta potential as a novel diagnostic tool for preeclampsia.

OBJECTIVE: To determine the zeta potential of erythrocyte and its association with morphological changes during preeclampsia so as to use it as a diagnostic tool to determine this pregnancy related complication. METHODS: This retrospective study included 502 pregnant women. Blood samples were collected in 5% dextrose solution from preeclampsia patients (n = 92) and normal pregnant women (n = 337). Zeta potential (ZP) of the erythrocyte was measured using Zeta meter System 4.0 equipped with zetameter-ZM4DAQ software using microscopically acquired video images. The experimental data was analysed using One Way analysis of variance using GraphPad Prism 5 Project software for Windows. RESULTS: In the present study, mean erythrocytic ZP of pregnant women in each trimester was found to be17.22 mV, 20.159 mV and 20.92 mV for the first, second and third trimester respectively. Whereas for control pregnant women it was found to be 21.07 ±â€¯0.3393 mV and for preeclampsia patients it was found to be 15.13 ±â€¯0.1393 mV which was significantly less than that of control pregnant volunteers along with structural deformity and increased osmotic fragility of erythrocytes. CONCLUSIONS: The data suggest that as pregnancy progresses there is increase in ZP values whereas in preeclampsia there is significant decrease in the ZP values below the normal level. This decrease in ZP values can be seen in early stages of pregnancy, which is difficult to diagnose by other available diagnostic tests. So, that early treatment can be started and development of further complications in mother as well as foetus can be avoided.