Enhancing Effect of Natural Oils as Permeation Enhancer for Transdermal Delivery of Diltiazem Hydrochloride through Wistar Rat Skin

摘要

The aim of the present investigation is to formulate and evaluate the biopharmaceutical behaviors of the matrix patch containing Diltiazem hydrochloride (DH) with an attempt of use of natural oils as permeation enhancers for transdermal applications. Transdermal patch prepared using 32 full factorial designs by solvent evaporation technique by incorporating propylene glycol as plasticizer and ethanol as solvent. Fourier transform infrared spectroscopy (FTIR) had employed to study drug and excipients incompatibility that showed the absence of any type of chemical interaction. Prepared patches evaluated for physico chemical parameters such as tensile strength, percent elongation, folding endurance, flatness, thickness, hardness, weight variation, percentage moisture loss and uptake, ex-vivo permeation study, in-vivo skin irritation study and stability study. The physicochemical and ex-vivo permeation studies indicated that Batch A2 containing HPMC K15M and psyllium in the ratio of 2:1 was better compare to all nine batches of factorial designs. Tensile strength, percent elongation and folding endurance found to be 4.48 kg/mm2, 21.84±0.335 and 384±3.21 respectively, which showed good mechanical property of prepared patch. Penetration enhancing capacity of natural oils (pumpkin seed oil, jojoba oil, tea tree oil, cumin oil, and linseed oil) was determined by performing ex-vivo study using wistar-rat skin. A maximum steady-state skin permeation flux of 239 μg/cm2/h achieved in the batch A2 which containing 20%w/w of pumpkin seed oil. The results of highest flux revealed that compare to all essential oils pumpkin seed oil enhance the permeation of drug through the skin. The release kinetics indicates that the release pattern was diffusion controlled and it follows higuchi and zero order kinetics. The skin irritation study performed on wistar-rats revealed that the patch was not irritating the skin after 24hours. Stability study performed according to ICH guideline and it showed that transdermal patch of DH containing natural oil was stable at accelerated conditions for six months. This research suggested that transdermal applications of DH improved patient compliance and very good alternative to oral administration of DH for the treatment of hypertension.