Objective: The main objective of the present investigation is to develop a sustained-release (SR) formulation to optimize the postprandial elevation of glucose level in type 2 Diabetic subjects using combination therapy. In the present research work, bilayer sustained release formulation of metformin hydrochloride (MFH) and gliclazide (GLZ), based on monolithic-matrix technology was developed and evaluated. Methods: The formulations of metformin hydrochloride layer and gliclazide layer that contain polyox WSR coagulant and different viscosity grades of hydroxyl propyl methylcellulose (HPMC) as sustained-release matrix were prepared by direct compression and wet granulation method respectively. The bilayer tablets were prepared after carrying out the optimization of metformin layer and evaluated for various pre-compression and post-compression parameters. For the best formulation selected on basis of in vitro evaluation of tablets, Fourier-transform infrared spectroscopy (FT-IR) studies and comparison of in vitro dissolution profile of developed formulation with the innovator were performed. Results: Metformin hydrochloride and gliclazide showed sustained release of drug by diffusion mechanism and followed first-order kinetics. The best formulation of metformin hydrochloride (M7) and gliclazide (G8) show 99.93% and 99.65% of drug release in 24 h respectively. The similarity factor (f2) was 79.95 for metformin hydrochloride and 73.62 for gliclazide when compared with the innovator. Conclusion: The monolith diffusion-controlled bilayer tablets of metformin hydrochloride and gliclazide offer improved patient compliance and convenience with better postprandial hyperglycemic control with once-a-day dosing. The sustained release of the drug up to 24 h regulate antidiabetic activity round the clock with minimal side effects.
Sacubitril and valsartan combination is a member of a new class of agents called angiotensin receptor-neprilysin inhibitors (ARNI’s) which combine neprilysin inhibitor and angiotensin receptor blocker (ARB). It is currently indicated for treating patients with heart failure with reduced ejection fraction (HFrEF) in place of an angiotensin-converting enzyme (ACE) inhibitor or ARB alone. The aim of present investigation is to develop a simple UV spectrophotometric method for the determination of sacubitril and valsartan combination in its pure form and pharmaceutical tablet formulations in 0.1N HCl (pH 1.2) and pH 6.8 phosphate buffer, and further to validate the developed method. The combination in bulk was estimated at λmax of 253 nm in 0.1N HCl and pH 6.8 phosphate buffer. The observed λmax was close to the calculated λmax predicted using Woodward Fieser rules. The method was validated using analytical parameters like linearity, precision, and accuracy as per guidelines laid down by International Conference on Harmonization (ICH). Beer’s law was obeyed in the concentration range of 1–20 μg/mL in both media with correlation coefficient value of 0.999. The accuracy was found between 99-101% in both media. The method showed good reproducibility with % RSD values less than 2. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.5353 μg/mL, 1.6222 μg/mL in 0.1N HCl and 0.395 μg/mL, 1.198 μg/mL in pH 6.8 phosphate buffer respectively indicating its sensitivity. Molar absorptivity of the drug was found to be 3.84x104, 3.68x104 L mole-1 cm-1 and Sandell’s sensitivity values were found to be 0.0249 and 0.025 μg cm-1/0.001 absorbance unit in 0.1 N HCl and pH 6.8 phosphate buffer respectively. The assay values of the drugs in pharmaceutical dosage forms were also found close to the labelled claim. The results demonstrated that the procedure is accurate, precise, and reproducible besides being simple, economical, and less time consuming and hence, suitably applied for routine analysis of sacubitril and valsartan combination in bulk, marketed tablet dosage forms and in vitro dissolution samples.
Sacubitril-valsartan supramolecular complex (SVSC), a first-in-class Angiotensin Receptor Neprilysin Inhibitor has been approved as safe and effective treatment for Heart Failure with Reduced Ejection Fraction and reduce the risk of cardiovascular death and re-hospitalization in patients with striking rise in blood pressure during early morning hours. As the cardiovascular events are well associated with circadian rhythms, chronotherapeutic drug delivery of SVSC at bedtime (around 10 p.m.) may be a potential approach. Aim and objective of present investigation is to develop chronotherapeutic drug delivery system of SVSC using natural gums by compression coating technique that is appropriate in achieving predetermined lag time of 5-6 hours followed by maximum drug release within 1 hour to attain the required C max when the disease condition is at peak. Initially the core tablets were optimized which completely released the drug in 25 minutes. The optimized core tablets were subjected to compression coating with different ratios of hupu gum, lannea gum and channeling agent for preparation of chronotherapeutic tablets. The optimized compression coated tablets complied with the official and other requirements of tablets. Differential scanning calorimetry and Fourier transformed infrared spectroscopy studies confirmed the drug and excipient compatibility. Among all formulations, Compression coated Tablets CCT3 met all the objectives of present investigation and hence, selected as optimized compression coated tablet suitable for chronotherapeutic drug delivery of SVSC in patients with heart failure.
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