Date of Award
Master of Science in Pharmaceutical Sciences
M. Serpil Kislalioglu
Current trend in evaluating dermatological formulations is shifting towards measuring the retention of drugs in the skin rather than flux through the skin. This study was undertaken to emphasize the importance of drug retention and to investigate possible factors which affect it.
An in vivo hairless rat model was used in this study to evaluate the effect of 26 vehicles on the local drug delivery to the skin layers. For this purpose, two model drugs, 3H-Hydrocortisone (HC) and 3H-triamcinolone acetonide (TAC), were used. Vehicles selected belonged to seven different classes including glycols, polyglycols, alcohols, esters, glycerides, mixed commercial vehicles and enhancers.
Solubilities of HC and TAC were determined in these vehicles using an HPLC method. The solubility data showed large ranges, 1912 fold for HC and 2297 for TAC, indicating a need to evaluate the influence of solubility on the skin uptake of these drugs.
In vivo retention studies were carried out in the hairless rat model using the "finite dose" approach. The drug uptake in the tissue was expressed in terms of μg of drug per gm of tissue and percent of applied dose retained in the skin layer. These data were then categorized into various classes of the vehicles used and the following findings were observed:
- Retention of HC and TAC in the epidermis and dermis was affected dramatically by the choice of vehicles.
- The overall rank orders and ranges were different for epidermal and dermal retention for both drugs indicating that the vehicle effects are different for the epidermis and dermis.
- In most cases the rank orders and ranges within different classes of vehicles was different for both drugs.
- Ratios of epidermal to dermal differently for HC and TAC. retention ranked differently for HC and TAC.
The foregoing observations e.g. differing rank orders and ranges, lead us to recommend the use of retention data instead of flux data in screening vehicles for optimizing dermatological formulations for these two drugs.
Marathe, Sudhanva R., "SYSTEMATIC STUDIES TO EVALUATE THE EFFECTS OF VEHICLES ON THE IN VIVO DRUG DELIVERY TO THE SKIN" (1994). Open Access Master's Theses. Paper 264.