Effect of HPMC concentration on crystal habit of nifedipine

Crystal habit can have profound influence on pharmaceutical properties. A study of the underlying mechanisms of interaction is crucial for understanding the foremost reasons responsible for alteration of crystal habit by additives. The effect of different concentrations of hydroxypropyl methylcellulose (HPMC) on nifedipine (Nif) crystal growth was studied wherein, an enhancement in aspect ratio was observed with an increase in concentration of HPMC. A similar pattern in aspect ratio was also observed using molecular dynamics (MD) simulation. The increase in the area of a specific facet was observed along with an increase in HPMC concentration, resulting in modification of the habit from near cubical (without HPMC) to plate shape (0.6% w/v HPMC). The dissolution rate of the re-crystallized Nif habits (dissolution medium 0.05% v/v Tween 20) was in the order of Nif-0 (Nif without HPMC) > Nif-2 (Nif from 0.2% w/v HPMC) > Nif-4 (Nif from 0.4% w/v HPMC) > Nif-6 (Nif from 0.6% w/v HPMC). The reduction in dissolution rate of Nif-6 was statistically significant (p < 0.05) when compared with Nif-0. Contact angle values (wetting properties) and surface free energy values in three solvents of different nature successfully supported the habit modification and the order of dissolution rate. Liquid chromatography-mass spectroscopy (LC-MS) was used to confirm the absence of HPMC incorporated in crystals or deposited on the surface. It was observed from the facet specific surface area values that HPMC induced a remarkable reduction in the growth on all crystal faces except {1 1 0}. The facet {1 1 0} was non-polar in nature as concluded from surface chemistry studies and resulted in a decrease in the dissolution rate of the crystal grown with higher HPMC concentration, where {1 1 0} occupied the crystal as a major facet.