FORMULATION AND EVALUATION IN VITRO A MATRIX TYPE OF KETOTIFEN FUMARATE TRANSDERMAL PATCHES FOR ALLERGIC DISEASES

  • Lama Hamdan Department of Pharmaceutical Technology, Faculty of Pharmacy, Damascus University, Damascus, Syria.
  • Jamila Husian Department of Pharmaceutical Technology, Faculty of Pharmacy, Damascus University, Damascus, Syria.

Abstract

 

 Objective: Transdermal patches of Ketotifen fumarate (KT) were developed for prolonged effect of the drug, and to protect the patient from allergic symptoms associated with asthma and other allergic diseases.

Methods: Matrix type patches were prepared by solvent casting technique using different types of polymers: Hydroxy propyl methyl cellulose (HPMC K15M) and ethyl cellulose to formed the matrix of the patch in different ratios, emulsifying agents were added as a penetration enhancers (Span 60, Tween 60, Cremophor EL) in a ratio 0.025% w/v to the matrix, 10% v/v of glycerin was added as plasticizer to 10 ml of chloroform:methanol (1:1). The drug matrix film was casted on a polyvinyl alcohol backing membrane. All patches were evaluated for physical proprieties, thickness uniformity, folding endurance, moisture uptake, moisture content, drug content, uniformity of weight, content uniformity, in vitro drug release, and kinetic models. Differential scanning calorimetry was used to characterize physical mixtures of KT and the different used excipients.

Results: The results showed that the prepared patches had acceptable physical properties. The drug substance was released well. Adding the penetration enhancers delayed the release of the drug from the matrix in all the prepared formulas, formula A2 that having no enhancer, showed maximum amounts of drugs release (90.06±0.9)% for 24 hrs. However, adding penetration enhancers decreased the amount of the drug release, formula B2 having Tween 60 as a penetration enhancer, showed the maximum release of the drug (87.78±0.88)%, and formula B3 having Cremophor EL showed the minimum release of the drug (79.13±1.58) at the end of 24 hrs dissolution study. The release of the drug from all formulations was followed by Korsmeyer-Peppas pattern with n>0.45 indicating that drug release from matrix was mainly happened by swallowed and diffusion (non- Fickian pattern).

Conclusion: Optimized formula A2 containing the maximum amounts of HPMC K15M showed a controlled release of the drug over 12 hrs, and it identified as a successful formulation for this study.

Keywords: Transdermal matrix patch, Ketotifen fumarate, Hydroxypropyl methylcellulose K15M, Ethyl cellulose, Span 60, Tween 60, Cremophor EL, Solvent casting technique.

References

1. Incidence R, Allergic OF. Review articles advances in immunology. N J Med 2001;344(1):30-7.
2. Elbehairy DM, Osman R, Sammour O. Inhaled taste masked spray dried ketotifen microparticles formulation, characterization and in vitro pulmonary deposition. Int J Pharm Pharm Sci 2016;8(6):166-74.
3. El-kommos ME, El-gizawy SM, Atia NN, Hosny NM. Analysis for commonly prescribed non-sedating antihistamines. Anal Chem Res 2015;3:1-12.
4. Cannon J, RanadeV. Transdermal drug delivery. In: Drug Delivery System. 3rd ed. Boca Raton: CRC Press; 2011. p. 243, 304.
5. Taylor K, editor. Topical and transdermal drug delivery. Aulton’s Pharmaceutics: The Design and Manufacture of Medicines. 4th ed. Edinburgh: Churchill Livingston; 2013. p. 676-97.
6. Kandavilli S, Nair V, Panchagnula R. Polymers in transdermal. Pharm Technol 2002;1195-206.
7. Allen VL, Nicholas G, Howard C. Transdermal drug delivery system. In: Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. 10th ed. USA: Lippincott William & Wilkins; 2011. p. 342-62.
8. Yousuf M, Ahmad M, Usman M, Ali I. Ketotifen fumarate and salbutamol sulphate combined transdermal patch formulations: In vitro release and ex vivo permeation studies. Indian J Pharm Sci 2013;75:569-77.
9. Patel NA, Patel NJ, Patel RP. Design and evaluation of transdermal drug delivery system for curcumin as an anti-inflammatory drug. Drug Dev Ind Pharm 2009;35(2):234-42.
10. Park JB, Kang CY, Kang WS, Choi HG, Han HK, Lee BJ. New investigation of distribution imaging and content uniformity of very low dose drugs using hot-melt extrusion method. Int J Pharm 2013;458(2):245-53.
11. Khushbu K, Kumar SA, Kant SG, Swaraj P. Transdermal drug delivery of salbutamol sulphate with different. Concentration of polymers. Int J Res Pharm Sci 2011;1(3):50-65.
12. Kshirsagar SJ, Bhalekar MR, Mohapatra SK. Development and evaluation of carvedilol-loaded transdermal drug delivery system: In-vitro and in-vivo characterization study. Drug Dev Ind Pharm 2012;38:1530-7.
13. Mittal A, Sara US, Ali A, Mohammed A. Design, development, physicochemical, in vitro and in vivo evaluation of monolithic matrix type transdermal patches containing nitrendipine. Pharm Dev Technol 2009;14:422-34.
14. Ravichandiran V, Manivannan S. Innovare academic sciences,wound healing potential of transdermal patches containg bioactive fraction from the bark of ficus pacemosa. Int J Pharm Pharm Sci 2015;7(6):326-32.
15. Fat H. In: Beck DC, editor. European Pharmacopeia. 7th ed. Germany: WHO; 2011. p. 234.
16. Sayeed MA, Farhad FM, Tareq SM, Islam N, Siddique SA, Das D. A study of in-vitro interaction of ketotifen fumarate with domperidone at different gastric and intestinal pH. Russ Open Med J 2014;3(2):5.
17. Clas S, Dalton CR, Hancock BC, Dalton CR, Hancock BC. Differential scanning calorimetry: Applications in drug development. Pharm Sci Technol Today 1999;2:1-8.
18. Karakatsani M, Dedhiya M, Plakogiannis FM. The effect of permeation enhancers on the viscosity and the release profile of transdermal hydroxypropyl methylcellulose gel formulations containing diltiazem HCl. Drug Dev Ind Pharm 2010;36:1195-206.
Statistics
204 Views | 355 Downloads
Citatons
How to Cite
Hamdan, L., and J. Husian. “FORMULATION AND EVALUATION IN VITRO A MATRIX TYPE OF KETOTIFEN FUMARATE TRANSDERMAL PATCHES FOR ALLERGIC DISEASES”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 10, no. 10, Sept. 2017, pp. 327-33, doi:10.22159/ajpcr.2017.v10i10.20123.
Section
Original Article(s)