Nifedipine

Elevated bioavailability is an advantage for most of the poorly soluble drugs. The present scenario of research investigation is concentrated on different techniques to alter the solubility characteristics of weakly soluble drugs and crystallization phenomenon is one amongst them. The low solubility problem can be solved by changing the crystal habit of drug. So, in the present research an attempt has been made to modify the solubility characteristics of Nifedipine, an anti-hypertensive drug, using solvent change method, Solvent evaporation technique and solvent change precipitation technique. Among them solvent change method gave a better formulation (NIF-MC-6) showing better dissolution (91.36% at the end of 240mins) as compared to pure drug and micro-crystals formulated using other methods. The formulated crystals of Nifedipine were subjected to various physico-chemical parameters like size distribution, solubility studies, in-vitro dissolution studies, drug content, FT- IR, DSC, crystallographic studies by PXRD and crystal morphology by SEM studies. The micro-crystals produced with PVPK30 and chloroform. FT-IR Results showed that there was no chemical interaction between the drug, solvent and the stabilizer. PXRD of micro-crystals showed higher peak height than pure drug indicating that crystal habit modification occurred in the micro-crystals without any polymeric changes and were found to be smaller in size than pure drug and free from any interactions. SEM studies indicated that the crystals are present in rectangular and square shape. The DSC curve showed that Nifedipine appeared an endothermic peak at about 1740C corresponding to its melting. However, the crystals prepared with PVP K30 shows shift of endothermic peak towards lower temperature at 170.820C respectively, dictating decreased melting point of the drug in the formed crystals, which accounted for increased solubility of the drugs.

In the present study Liquisolid preparations of nifedipine were prepared by dissolving the drug in a chosen non-toxic, non-volatile solvent and adsorbing onto carrier materials. Various carrier and coating materials were employed in the study. Avicel PH 101 was used as the carrier material and Aerosil was used as the coating material as conventional liquisolid systems, apart from that novel excipients like Fujicalin® and Neusilin® were employed and their effects on the dissolution rate of the drug was studied. The results showed that the solubility of the drug was maximum in polysorbate 20 amongst the selected non volatile solvents i.e. Polyethylene glycol 400, 600, propylene glycol, glycerol and Tween 20. The solution of nifedipine in polysorbate 20 was found to be stable for at least 15 days. It was also found out that Fujicalin® and Neusilin® were much better adsorbents as compared to microcrystalline cellulose. Fujicalin® enhanced the drug release where as Neusilin® when used as an adsorbent retarded the rate of release. Liquisolid systems in general showed enhanced dissolution profile as compared to their directly compressed counterparts. The prepared liquisolid systems were subjected to tests such as FT-IR spectroscopy, differential scanning calorimetry (DSC) and X-Ray crystallography (PXRD) for evaluating the physiochemical properties of the drug in the liquisolid systems. Differential scanning calorimetry and X-Ray crystallography conclusively proved the loss of crystalline structure of nifedipine in the liquisolid systems, thus confirming the enhanced solubility. The optimized liquisolid compact was then compared with commercially available soft gelatine capsules.