POLYVINYLPYRROLIDONE K30

Background: Amlodipine is a third-generation dihydropyridine antihypertensive that blocks calcium on calcium channels used frequently in hypertension and angina. It has even been listed by WHO as an Essential Medicine. Although very practical, it belongs to the Biopharmaceutical Classification System (BCS Class) II - the drug is very permeable across the intestinal wall but very low water solubility. Even the low solubility is the slowest step in absorption which may lead to the release of tablets being not fully done, inconsistent bioavailability between different patients and reliance on food. Consequently, by enhancing solubility of amlodipine we desire to make the administration of amlodipine more effective orally.
Purpose: The purpose of this work was the development, characterization, and testing of solid dispersions (SDs) of amlodipine with Polyvinylpyrrolidone (PVP K30). We thought that the method would help us to change the drug which is not soluble in large quantities but exists as crystals to a high- energy, highly soluble amorphous one. The research rigorously investigated system of varying drug- polymer ratios and characterized the optimally dispersed system completely, as a solubility was demonstrated and the in-vitro rate of solubility was significantly increased.
Material and Methods: Amlodipine solid dispersions through solvent evaporation method were prepared by us. A common organic solvent (ethanol) was used to dissolve the drug as well as the hydrophilic carrier, PVP K30. A rotary evaporator was then used to remove the solvent under reduced pressure leaving a mass of solid. This mass was dried, ground and sieved. Five ratios of drug-polymer weight were made: 1:1, 1: 2, 1:3, 1:4 and 1:5. Lastly, all Solid dispersion had their apparent aqueous solubility determined. And lastly we pressed this optimized powder into tablet form and compared the drug release of this tablet in in-vitro with that of a normal tablet in a dissolution experiment. Results: There was distinct polymer-dose-dependent increase in aqueous solubility of Mamlodipine in the solid dispersions relative to pure, unprocessed amlodipine drug. This ratio was the best solubility enhancer with the highest level of 1:5 (drug: polymer), and it was determined to completely analyze. FTIR of 1:5 Solid dispersion showed the typical peaks of the amlodipine and PVP K30, and no new peak or significant change, meaning strong chemical interaction. The most important was the Differentiated Scanning Calorimetry (DSC) thermogram, which indicated the total loss of the sharp endothermic melting point of crystalline amlodipine, which confirmed the drug had been transformed to a molecularly dispersed or amorphous form. Most importantly, the 1:5 solid dispersion to tablets discharged the drug far quicker and more certainly in-vitro when compared to the control tablets to the pure drug.
Conclusion: This experiment proves the application of PVP30 as a hydrophilic carrier in a solvent evaporation solid-dispersion method is an efficient approach to increase the solubility and dissolution rate of the poorly water-soluble amlodipine drug. The 1:4 optimization resulted in the drug being altered to a stable and amorphous form, thus a significantly better release profile. This method presents a good avenue towards the generation of novel oral dosage shapes of amlodipine that may confer improved bioavailability and dependable therapeutic results