ENHANCED PERCUTANEOUS PERMEABILITY OF ACYCLOVIR BY DMSO FROM TOPICAL GEL FORMULATION
Abstract
The aim of this study was to investigate the effect of DMSO on the permeation of acyclovir in the form of topical gel formulations. Different formulations were prepared containing carbopol 934P, acyclovir (1 % w/w) and selected concentration of DMSO (0 to 10% w/w) to evaluate drug content, spreadibility, pH, viscosity, and in-vitro permeation through mouse epidermis and porcine skin. FTIR spectrometry was used to investigate physical state of drug in the gel formulations. The mechanisms of drug permeation were evaluated by FTIR spectrophotometer and histopathological studies. The carbopol 934P gel was found to contain 95.62 to 98.89 % of acyclovir and spreadibility was found in the range of 10.75 to 11.75 g.cm/sec. The pH of all formulations was found near to the skin pH value. The viscosity of the formulations was found inversely proportional with drug permeation. A maximum permeation flux of acyclovir (463.42±36.41µg/cm2.h) through porcine skin was observed with an enhancement ratio of 1.55, when DMSO was incorporated at a concentration of 10%w/w in gel system. The FTIR spectra revealed the absence of drug-polymer interaction. From FTIR spectroscopy and histopathological studies it was evident that the permeation of acyclovir, across mouse and porcine skin, were increased in presence of DMSO which can be attributed to the partial extraction of lipids in the stratum corneum. The results suggest that DMSO may be useful for enhancing the skin permeability of acyclovir from transdermal therapeutic system containing carbopol 934P gel as reservoir.
Keywords:
Topical Gel, Acyclovir, carbopol 934PDOI
https://doi.org/10.25004/IJPSDR.2009.010104References
2. Collins P, Baue, PJ. The activity in-vitro against herpes virus of 9-(2-hydrozyethoxymethyl) guanine (Acycloguanosine). A new antiviral agent. Journal of Antimicrobilogy and chemotherapy 1979; 5; 431-446.
3. DeClercq E., Descamps J, Verhelst GA, Walker RT, Jones AS, Torrence PF, Shugar D. Comparative efficacy of antiherpes drugs against different strains of herpes simplex virus, Journal of Infections Diseases 1980; 141; 563-574.
4. Frumar PA, St. Clair MH, Spector T. Acyclovir triphosphate is a suicide inactivator of the herpes simplex virus DNA polymerase. The Journal of Biological Chemistry 1984; 259; 9575-9579.
5. Reardon JE, Sector T. Herpes simplex virus type I DNA polymerase: mechanism of inhibition by acyclovir triphosphate. The Journal of Biological Chemistry 1989; 264; 7405-7411.
6. Shao Z, Mitra AK. Bile salts-fatty acid mixed micells as nasal absorption promoters: III. Effect of nasal transport and enzymatic degradation of acyclovir prodrug. Int. J. Pharm.1994; 11; 243-250.
7. Shojaei AH, Berner B. Transbuccal delivery of acicyclovir: in-vitro determination of routes of buccal transport. Pharm. Res. 1998; 15; 1182-1187.
8. Franklin KA, Gray PM, Andy GM, Marc BB. Effect of abrasion induced by rotating brush on the skin penetration of routes with varying physicochemical properties. Eur. J.Pharm. Biopharm. 1007; 10; 1016-1027.
9. B. P. Pharmaceutical Codex, 1994, 711-713.
10. Bergstrom CAS, Strafford M, Lazorova L, Avdeef A, Luthman K, Artursson P. Absorption classification of oral drugs based on molecular surface properties. J. Med. Chem. 2003; 46(4); 558-570.
11. Handgraft J, Majella EL. Skin permeation: The years of enlightment. Int J Pharmaceutics 2005; 305; 2-12.
12. Naik A, Yogeshvar NK, Richard HG. Transdermal drug delivery: Overcoming the skin’s barrier function. PSTT 2000; 3(9); 318-326.
13. Chandar A, Sharma PK. Transdermal delivery of ketorolac. The Pharmaceutical Scoiety of Japan 2009; 129(3); 373-379.
14. Pathan IB, Setty CM. Chemical permeation enhancers for transdermal delivery system. Tropical Journal of Phrmaceutical Research 2008; 8(2); 173-179.
15. Ammar HO, Ghorab M, El-Nahhas SA, Kamel R. Evaluation of chemical penetration enhancer for the transdermal delivery of aspirin. Asian Journal of Pharmaceutical Sciences 2007; 2(3); 96-105.
16. Aguilar JS, Roy D, Ghazal P, Wagner EK. Dimethyl sulfoxide blocks herpes simplex virus-1 productive infection in vitro acting at different stages with positive cooperativity. Application of micro-array analysis. BMS Infectious Diseases. www. biomedcentral.com
17. Jain S, Padsalg BD, Patel AK, Moale V. Formulation development and evaluation of fluconazole gel in various polymer bases formulation development and evaluation of fluconazole gel in various polymer bases. Asian Journal of Pharmaceutics 2007; 1; 63-68.
18. Krishnaiah, YSR, Satyanarayana V, Karthikeyan RS. Penetration enhancing effect of methanol on the percutanous absorption of nicardipine hydrochloride from HPC gel through excised rat epidermis. Pharm. Dev. Tech. 2002; 7; 305-316.
19. Higuchi WI. Analysis of data on the medicament release from ointments. J. Pharm Sci.1962; 51; 802-804.
20. Yumune MA. Williams AC, Berry BW. Terpenes penetration enhancers in propylene glycol/water co-solvent system effictiveness and mechanism of action. Journal of Pharmacy and Pharmacology 1995; 47; 978-989.
21. Williams AC and Barry BW. Terpenes and lipid-protein partitioning theory of skin penetration enhancement. Pharmaceutical Resesarch 1991; 8; 17-24.
22. Roberts MS, Cross SE and Pellet MA. Skin Transport, In Walters KA. Eds., Dermatological and Transdermal Formulations, Marcel Dekker, New York, 2002, pp.89.
23. Panigrahi L, Ghosal SK, Pattnaik S, Malarana L, Barik BB. Effect of permeation enhancers on the release and permeation kinetics of lincomycin hydrochloride gel formulations through mouse skin. Ind J Pharm Sci. 2006; 68(2); 205-211.
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