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.

Impact of rasagiline nanoparticles on brain targeting efficiency via gellan gum based transdermal patch: A nanotheranostic perspective for Parkinsonism.

Rasagiline mesylate is used as first line agent for early management of Parkinson's disease but its water soluble nature creates hurdles to cross blood brain barrier also its low oral bioavailability and rapid elimination requires frequent dosing. Thus present study aims to prepare rasagiline mesylate-nanoparticles (RM-NPs) loaded gellan gum transdermal film for non-invasive; self-administration in elderly patients. PLGA coated RM-NPs prepared by solvent evaporation technique were incorporated into film prepared by solvent casting method. Optimized films with 1.127 g gellan gum and 1.962 % linoleic acid showed enhanced ex-vivo diffusion over a period of 72 h. Comparative pharmacokinetic study revealed increased bioavailability of rasagiline on transdermal application compared to oral route. In-vivo anti-Parkinson activity estimated by behavioural and biochemical analysis indicate reserpine to interfere with monoamine storage hence resulting in development of akinesia and PD-like symptoms in rats. Brain targeting monitored by gamma imaging showed effective brain drug uptake from transdermal film which was also supported by increased brain targeting efficiency estimated from biodistribution study. Thus, the data support efficacy of gellan gum film to target drug to brain region compared to oral route and hence can be employed as a convenient approach for long-term treatment of Parkinson's disease in elderly patients.

Enhanced transdermal permeation and anti-inflammatory potential of phospholipids complex-loaded matrix film of umbelliferone: Formulation development, physico-chemical and functional characterization.

In the present study, umbelliferone - phospholipids complex - loaded matrix film (UPLC - MF) was developed with a goal of improving transdermal permeation and anti-inflammatory potential of umbelliferone (UMB). Umbelliferone - phospholipids complex (UPLC) was prepared using solvent evaporation method. UPLC-MF was prepared by simple and reproducible solvent casting method. Prepared UPLC and UPLC-MF were both physico-chemically characterized by Fourier transforms infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), proton nuclear magnetic resonance spectroscopy (1H NMR), weight variation, thickness, tensile strength, folding endurance, % elongation, moisture content and uptake Functional characterization of UPLC and UPLC-MF was carried out by solubility analysis, in vitro dissolution, diffusion, and ex vivo permeation via dialysis and biological membrane. UPLC - MF was also evaluated for in vivo anti-inflammatory activity using carrageenan-induced Albino rat paw model. Design-based optimal values for formulation and process variables of UPLC were observed to be 1:1.78, 50 °C and 2 h, respectively. Physico-chemical characterization confirmed the formation of the complex and the film. UPLC demonstrated a higher aqueous solubility (~11-fold), compared to pure UMB. Rate and extent of dissolution of UMB from UPLC was enhanced significantly to that of pure UMB. Compared to UMB-MF, the diffusion and permeation rate of UMB from UPLC-MF enhanced significantly. The UPLC - MF improved the anti-inflammatory potential of UMB by significant enhancement of edema inhibition (%), compared to UMB-MF. The obtained results showed that the present combined formulation system could be employed as a promising strategy for improving transdermal permeation of UMB.