FEASIBILITY OF PALIPERIDONE FOR TRANSDERMAL THERAPEUTIC SYSTEMS: EX VIVO PERMEATION KINETIC STUDIES OF DRUG THROUGH RAT ABDOMINAL SKIN
Objective: The main objective of the current research study was to investigate the effect of various permeation enhancers on the skin permeation of paliperidone for transdermal therapeutic systems (TTS).
Methods: A part of pre-formulation studies was performed to authentication of the drug by determining the melting point, solubility, partition coefficient (PC), attenuated total reflection-Fourier transform infrared, differential scanning calorimetry, and its purity by reversed-phase high-performance liquid chromatography. Ex vivo permeation kinetic study for paliperidone alone and with 5% concentration of permeation enhancers hyaluronidase, dimethylsulfoxide (DMSO), groundnut oil, and tween 80 was conducted in modified Franz diffusion cell through rat abdominal skin as a barrier. The receptor phase containing 20% polyethylene glycol 400 in normal saline was maintained at 37°C. The steady-state flux was obtained to calculate permeability coefficient, enhancement ratio (ER), and the cumulative amount of drug permeated at 12 h.
Results: The pre-formulation study results indicated that the received pure drug was authentified as paliperidone and its purity at par with official pharmacopeia. The PC of the drug was found to be 1.916±1.07, indicated that the drug to be lipophilic. The ex vivo permeation study results showed that the enhancement effect of some permeation enhancers on paliperidone was as follows: Hyaluronidase>DMSO>groundnut oil>tween 80. Hyaluronidase has high permeation enhancing activity with the highest permeation flux of 12.038 μg/cm2/h, and the cumulative amount of drug permeated was 212.760 μg/cm2. The ER of hyaluronidase was 3.69 folds higher than control.
Conclusion: The results of the present research study attributed that hyaluronidase was a potential permeation enhancer which would be included in the TTS of paliperidone.
2. Pastore MN, Kalia YN, Horstmann M, Roberts MS. Transdermal patches: History, development and pharmacology. Br J Pharmacol 2015;172:2179-209.
3. Wilson EJ. Three Generations: The Past, Present, and Future of Transdermal Drug Delivery Systems. USA: Pharmcon. SC; 2011.
4. U.S. Food and Drug Administration. Approved Drug Products with Therapeutic Equivalence, Evaluations. Rockville, MD, USA: U.S. Food and Drug Administration; 2016.
5. Singh I, Morris AP. Performance of transdermal therapeutic systems: Effects of biological factors. Int J Pharm Investig 2011;1:4-9.
6. Paudel KS, Milewski M, Swadley CL, Brogden NK, Ghosh P, Stinchcomb AL, et al. Challenges and opportunities in dermal/ transdermal delivery. Ther Deliv 2010;1:109-31.
7. Willams AC, Barry BW. Permeation enhancer. Adv Drug Deliv Rev 2012;64:128-37.
8. Karande P, Mitragotri S. Enhancement of transdermal drug delivery via synergistic action of chemicals. Biochim Biophys Acta 2009;1788:2362-73.
9. Haque T, Talukder MMU. Chemical enhancer: A simplistic way to modulate barrier function of the stratum corneum. Adv Pharm Bull 2018;8:169-79.
10. Ameen D, Michniak-Kohn B. Transdermal delivery of dimethyl fumarate for Alzheimer’s disease: Effect of penetration enhancers. Int J Pharm 2017;529:465-73.
11. Sweetman SC, editor. Martindale: The Complete Drug Reference. 34th ed. London: Pharmaceutical Press; 2002.
12. Alphs L, Fu DJ, Turkoz I. Paliperidone for the treatment of schizoaffective disorder. Expert Opin Pharmacother 2016;17:871-83.
13. Peuskens J, Rubio G, Schreiner A. Dosing and switching of paliperidone ER in patients with schizophrenia: Recommendations for clinical practice. Ann Gen Psychiatry 2014;13:10.
14. Prabhakar D, Divya A, Prathyusha R, Kumar K. Augmentation of dissolution profile of poorly soluble paliperidone by employing liquisolid technology. Int J PharmTech Res 2014;6:710-9.
15. Venkatasairam K, Gurupadayya BM, Vishwanathan BI, Chandan RS. Determination of octanol-water partition coefficient of novel coumarin based anticancer compounds by reversed-phase ultra-fast liquid chromatography. Int J Pharm Pharm Sci 2017;9:98-104.
16. Akram MR, Ahmad M, Abrar A, Sarfraz RM, Mahmood A. Formulation design and development of matrix diffusion controlled transdermal drug delivery of glimepiride. Drug Des Devel Ther 2018;12:349-64.
17. Takeuchi H, Mano Y, Terasaka S, Sakurai T, Furuya A, Urano H, et al. Usefulness of rat skin as a substitute for human skin in the in vitro skin permeation study. Exp Anim 2011;60:373-84.
18. Davaran S, Rashidi MR, Khandaghi R, Hashemi M. Development of a novel prolonged-release nicotine transdermal patch. Pharmacol Res 2005;51:233-7.
19. Subhash PG, Dinesh BM, Ravikumar M. Feasibility of lercanidipine hydrochloride for TDDS: Permeation kinetic study in presence of various penetration enhancers. Int J Pharm Pharm Sci 2011;3:103-7.
20. Mori NM, Patel P, Sheth NR, Rathod LV, Ashara KC. Fabrication and characterization of film-forming voriconazole transdermal spray for the treatment of fungal infection. Bull Fac Pharm Cairo Univ 2017;55:41-51.
21. Kumar S, Randhawa JK. Solid lipid nanoparticles of stearic acid for the drug delivery of paliperidone. RSC Adv 2015;5:68743-50.
22. Aggarwal G, Dhawan S, Harikumar SL. Formulation, in vitro, and in vivo evaluation of matrix-type transdermal patches containing olanzapine. Pharm Dev Technol 2013;18:916-25.
23. Samanta MK, Dube R, Suresh B. Transdermal drug delivery system of haloperidol to overcome self-induced extrapyramidal syndrome. Drug Dev Ind Pharm 2003;29:405-15.
24. Chandrashekar NS, Shobha Rani RH. Physicochemical and pharmacokinetic parameters in drug selection and loading for transdermal drug delivery. Indian J Pharm Sci 2008;70:94-6.
25. Rajkumar M, Surendra G. Preparation and characterization of nanocrystals for solubility and dissolution rate enhancement of paliperidone using different hydrophilic carriers: In vitro-in vivo study. Asian J Pharm Clin Res 2018;4:393-8.
26. Pal C, Giri P. Surfactants as penetration enhancer in transdermal drug delivery system. Int J Res Rev 2017;4:104-16.
27. Rhein L, Robbins C, Fernee K. Surfactant structure effects on swelling of isolated human. J Soc Cosmet Chem 1986;37:125-39.
28. Pandey A, Mittal A, Chauhan N, Alam S. Role of surfactants as penetration enhancer in transdermal drug delivery system. J Mol Pharm Org Process Res 2014;2:2-7.
29. Nokhodchi A, Shokri J, Dashbolaghi A, Hassan-Zadeh D, Ghafourian T, Barzegar-Jalali M, et al. The enhancement effect of surfactants on the penetration of lorazepam through rat skin. Int J Pharm 2003;250:359-69.
30. Anyasor GN, Ogunwenmo KO, Oyelana OA, Ajayi D, Dangana J. Chemical analysis of groundnut oil (Arachis hypogaea). Pak J Nutr 2009;3:269-72.
31. Naik A, Pechtold LA, Potts RO, Guy RH. Mechanism of oleic acid-induced skin penetration enhancement in vivo in humans. J Control Release 1995;37:299-306.
32. Fujii M, Hori N, Shiozawa K, Wakabayashi K, Kawahara E, Matsumoto M, et al. Effect of fatty acid esters on permeation of ketoprofen through hairless rat skin. Int J Pharm 2000;205:117-25.
33. Mittal A, Sara UV, Ali A, Aqil M. Status of fatty acids as skin penetration enhancers-a review. Curr Drug Deliv 2009;6:274-9.
34. Aggarwal G, Dhawan S, Hari Kumar SL. Formulation, in vitro and in vivo evaluation of transdermal patches containing risperidone. Drug Dev Ind Pharm 2013;39:39-50.
35. Jain R, Aqil M, Ahad A, Ali A, Khar RK. Basil oil is a promising skin penetration enhancer for transdermal delivery of labetolol hydrochloride. Drug Dev Ind Pharm 2008;34:384-9.
36. Marren K. Dimethyl sulfoxide: An effective penetration enhancer for topical administration of NSAIDs. Phys Sportsmed 2011;39:75-82.
37. Lundborg M, Wennberg CL, Narangifard A, Lindahl E, Norlén L. Predicting drug permeability through skin using molecular dynamics simulation. J Control Release 2018;283:269-79.
38. Zafar S, Ali A, Aqil M, Ahad A. Transdermal drug delivery of labetalol hydrochloride: Feasibility and effect of penetration enhancers. J Pharm Bioallied Sci 2010;2:321-4.
39. Anigbogu AC, Williams AC, Barry BW, Edwards HM. Fourier transform raman spectroscopy of interactions between the penetration enhancer dimethyl sulfoxide and human stratum corneum. Int J Pharm 1997;155:241-50.
40. Panchagnula R. Transdermal delivery of drugs. Indian J Pharmacol 1997;29:140-56.
41. Girish KS, Kemparaju K. The magic glue hyaluronan and its eraser hyaluronidase: A biological overview. Life Sci 2007;80:1921-43.
42. Kong M, Chen XG, Kweon DK, Park HJ. Investigations on skin permeation of hyaluronic acid based nanoemulsion as transdermal carrier. Carbohyd Polym 2011;2:837-43.
43. Yang R, Wei T, Goldberg H, Wang W, Cullion K, Kohane DS, et al. Getting drugs across biological barriers. Adv Mater 2017;29:1606596.
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