methylcellulose and hydrocortisone-acetate

The influence of hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), polyvinyl pyrrolidone (PVP) and polyethylene glycol (PEG400) on the crystallization of hydrocortisone acetate (HA) was studied. Supersaturation was created by the cosolvent technique. Spontaneous nucleation was observed when no polymer was used as the additive. In the presence of the polymer, nucleation was delayed. The nucleation time decreased with increasing supersaturation at a particular polymer concentration and increased with increasing polymer concentration at a particular supersaturation. Habit modification from a well-defined polar prismatic morphology to a wing-shaped morphology was observed when HPMC was used as the additive. The effect of PVP and PEG400 on the morphology of HA was less pronounced compared to the cellulose polymers. The mechanism of nucleation retardation by the polymers is explained in terms of association of HA with the polymer through hydrogen bonding. The growth may be inhibited by the hydrodynamic boundary layer, in which the polymers accumulate as well as by the adsorption of the polymer onto the crystal surface. The habit modification of HA by HPMC is due to different extents of adsorption on different faces of the crystal, the extent of which is dependent on the hydrogen bonding functional groups that are exposed at each face of the crystal.

Topics: Crystallization; Gels; Hydrocortisone; Hydrogen Bonding; Lactose; Methylcellulose; Oxazines; Polyethylene Glycols; Povidone

A systematic investigation on the influence of two cellulose polymers, methyl cellulose (MC) and hydroxypropyl cellulose (HPMC) on supersaturation and permeation of hydrocortisone acetate (HA) is reported. Diffusion of HA from a 0.5% Carbopol gel across a model silicone membrane was investigated using the Franz-cell technique. At constant polymer concentration, the flux increases proportionally with the degree of saturation up to 4.8x but decreases thereafter. For a particular degree of supersaturation (4.8x), the flux increases with the concentration of polymer up to 1% and decreases at higher concentrations. The behaviour is found to be consistent with crystallisation experiments. The results suggest that optimisation of supersaturation and polymer content is necessary to achieve both high permeation rates and inherent stability.

Topics: Cellulose; Chromatography, High Pressure Liquid; Diffusion; Gels; Hydrocortisone; Membranes, Artificial; Methylcellulose; Permeability; Silicones; Solubility; Solvents

Factors affecting reduction in the permeation rate of nitrofurantoin and hydrocortisone acetate from methylcellulose solutions through a cellulose membrane were investigated. The factors evaluated were the effect of polymer agglomeration and whether the drugs formed a complex with the polymer. The influence of polymer agglomeration was evaluated by dynamic dialysis studies of nitrofurantoin dissolved in solutions of methylcellulose 400 cps, which agglomerates, and in methylcellulose 50 cps, which does not exhibit this behavior. Dialysis rates of this drug were measured as a function of polymer concentration, ionic strength, heating time prior to measurement, and temperature. The effect of polymer agglomeration on the permeation rates of hydrocortisone acetate was studied by varying the ionic strength of the drug-polymer solution. Complex formation studies were conducted for both drugs by the equilibrium dialysis method. Polymer agglomeration caused a substantial reduction in the dialysis rate of both drugs in methylcellulose 400 cps solutions. There was less reduction in the dialysis rate of nitrofurantoin with increased polymer concentration of methylcellulose 50 cps solutions, which was attributed to the increase in the bulk viscosity of the solution. There was no evidence of complex formation of the drugs with the polymers.

Topics: Chemical Phenomena; Chemistry; Dialysis; Hydrocortisone; Methylcellulose; Nitrofurantoin; Rheology; Solutions; Temperature; Viscosity