Stability of triptorelin in the presence of dermis and epidermis.
An important issue with respect to the transdermal delivery of peptides is their stability during transit through the epidermis and dermis before entry into the systemic circulation. The objective of the present study was to evaluate the effect of epidermal and dermal tissue on the stability of the luteinizing hormone releasing hormone superagonist, triptorelin. The decapeptide was dissolved in PBS (pH 7.4) and placed in contact with (i) heat separated epidermis (HSE), (ii) dermatomed skin (0.75 mm; DS) and (iii) full thickness skin (FTS) and the extent of peptide biotransformation monitored as a function of time by HPLC. The results showed that triptorelin was metabolized when in contact with each of the skin tissues. However, there were marked differences with respect to the extent of peptide degradation. Triptorelin was least stable in the presence of FTS. After 3 h exposure to HSE, DS and FTS, the extent of triptorelin degradation was 15.0+/-6.0%, 64.8+/-9.9% and 100%, respectively. After 24 h, further triptorelin degradation had occurred in the samples in contact with HSE and DS--with 51.3+/-6.0% and 87.8+/-4.4%, respectively, of the peptide being degraded. The chromatograms revealed the presence of a degradation peak at a higher retention time than the parent molecule--most probably the free acid.
Bachhav
Yogeshwar G
YG
School of Pharmaceutical Sciences, University of Geneva and University of Lausanne, 30 Quai Ernest Ansermet, 1211 Geneva, Switzerland.
Kalia
Yogeshvar N
YN
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D020405:Dermis / Q000378:metabolism*; D004355:Drug Stability; D004817:Epidermis / Q000378:metabolism*; D066298:In Vitro Techniques; D008954:Models, Biological; D013552:Swine; D013997:Time Factors; D017329:Triptorelin Pamoate / Q000378:metabolism*
D018931:Antineoplastic Agents, Hormonal; D017329:Triptorelin Pamoate