Čes. slov. farm. 2013, 62(1):19-27
Design and development of diltiazem hydrochloride transmucosal drug delivery system
- 1 Department of Pharmaceutics, MNR College of Pharmacy, Sangareddy-502294, Andhra Pradesh, India
- 2 Department of Pharmaceutics, Sultan-ul-uloom College of Pharmacy, Hyderabad, India
- 3 Institute of Pharmaceutical Technology, Sri Padmavathi Visva Vidyalayam, Tirupathi, India
Diltiazem hydrochloride is an antihypertensive agent which undergoes extensive first pass metabolism making it a possible candidate for buccal delivery. Diltiazem mucoadhesive buccal patches were prepared using HPMC, chitosan, PVP, PVA and carbopol. The physicochemical interactions between diltiazem and the polymers were investigated by FTIR and DSC, results revealed no interaction between drug and polymers. The patches were evaluated for various physicochemical parameters, in vitro release studies and ex vivo permeation through porcine buccal mucosa. Residual solvent content in patches was determined by gas chromatography and are largely below the tolerated limits. The formulations showed an extended release of the drug upto a period of 12 hours during ex vivo permeation and showed non Fickian drug release. Stability of the optimized formulation was investigated as per ICH guidelines and was found to be stable with respect to drug content and ex vivo permeation.
Keywords: diltiazem hydrochloride; buccal patches; residual solvents; mucoadhesion; in vitro drug release; ex vivo permeation
Received: November 27, 2012; Accepted: January 7, 2013; Published: January 1, 2013 Show citation
References
- Aungst B. J., Rogers M. J., Shefter E. Comparison of nasal, rectal, buccal, sublingual and intramuscular Insulin efficacy and the effects of a bile salt as absorption promoter. The J Pharmacol Exp Ther. 1998; 244, 23-27.
Go to original source...
- Lee W. E. Permeation enhancers for nasal drug delivery of protein and peptide therapeutics. Biopharm. 1990; 3, 22-25.
- Soyani A. P., Chein Y. W. Systemic delivery of peptides and proteins across absorptive mucosae. Crit Rev Therapy: Drug Carries System. 1996; 13, 85-184.
- Rathbone M. J., Hadgraft J. Absorption of drugs from the human oral cavity. Int J Pharm. 1991; 74, 9-24.
Go to original source...
- Squier C. A. The permeability of oral mucosa. Crit Rev Oral Biol Med. 1991; 2, 13-32.
Go to original source...
Go to PubMed...
- Gandhi R. E., Robinson J. R. Bioadhesion in drug delivery. Ind J Pharm Sci. 1998; 50, 145-152.
- Saisavam S., Muhammed M. H. Design and evaluation of Diltiazem Hydrochloride buccal patches. Ind J Pharm Sci. 2000; 62, 236-238.
- Verma P. R. P., Sunil S. I. Transdermal Delivery of Propranolol Using Mixed Grades of Eudragit: Design and in vitro and in vivo Evaluation. Drug Dev Ind Pharm. 2000; 26, 471-476.
Go to original source...
Go to PubMed...
- Pavankumar G. V., Ramakrishna V., William G. J., Konde A. Formulation and evaluation of buccal films of Salbutamol sulphate. Indian J Pharm Sci. 2005; 67, 160-164.
- Khanna R., Agarwal S. P., Ahuja A. Preparation and evaluation of buccal films of clotrimazole for oral candida infections. Indian J Pharm Sci. 1997; 59, 299-305.
- Nafee N. A., Boraie N. A., Ismail F. A., Mortada L. M. Mucoadhesive delivery systems II. Formulation and in vitro/ in vivo evaluation buccal mucoadhesive tablets containing water soluble drugs. Drug Dev Ind Pharm. 2004; 30, 995-1004.
Go to original source...
Go to PubMed...
- Ilango R., Kavimani S., Mullaichasam A. R., Jayakar B. In vitro studies on buccal strips of Glibenclamide using chitosan. Indian J Pharm Sci. 1997; 59, 232-235.
- Kulkarni U., Mahalingam R., Pather S. I., Li X., Jasti B. Porcine Buccal Mucosa as an In Vitro Model: Relative Contribution of Epithelium and Connective Tissue as Permeability Barriers. J Pharm Sci. 2009; 98, 471-483.
Go to original source...
Go to PubMed...
- Metia P. K., Bandyopadhyay A. K. In vitro Evaluation of Novel Mucoadhesive Buccal Tablet of Oxytocin Prepared with Diospyros Peregrina Fruits Mucilages, Yakugaku Zasshi. 2008; 128, 603-609.
Go to original source...
Go to PubMed...
- Agarwal V., Mishra B. Design, Development, and Biopharmaceutical Properties of Buccoadhesive Compacts of Pentazocine. Drug Dev Ind Pharm. 1999; 25, 701-709.
Go to original source...
Go to PubMed...
- Puranik S. B., Varun Pawar R., Lalitha N., Pai P. N., Rao G. K. Residual Solvent Analysis in Hydrochloride Salts of Active Pharmaceutical Ingredients. Pak J Pharm Sci. 2009; 22, 410-414.
- Stackler B., Christensen E. N. Quantitative Determination of Ethanol in Wine by Gas Chromatography. Amer J Enol Viticult. 1974; 25, 202-207.
Go to original source...
- Robert Schubert B. S., Ketel L. Gas Chromatographic Determination of Methylene Chloride in Aerosol air Sprays. J Soc Cosmet Chem. 1972; 23, 115-124.
- Kratochvil J., Holas J. A gas chromatographic method for the determination of acetic acid and lactic acid in rye sour. Cereal Chem. 1980; 57, 209-211.
- Al Saidan S. M., Krishnaiah Y. S., Patro S. S., Satyanaryana V. In Vitro and In Vivo Evaluation of Guar Gum Matrix Tablets for Oral Controlled Release of Water-soluble Diltiazem Hydrochloride. AAPS Pharm Sci Tech. 2005; 6 (1) Article 5. http://www.aapspharmscitech.org.
Go to original source...
Go to PubMed...
- Patel V. M., Prajapati B. G., Patel J. K., Patel M. M. Design and characterization of chitosan-containing mucoadhesive buccal patches of propranolol hydrochloride. Acta Pharm. 2007; 57, 61-72.
Go to original source...
Go to PubMed...
- Shojaei A. H., Zhou S. L., Li X. Transbuccal Delivery of Acyclovir (II): Feasibility, System Design, and In Vitro Permeation Studies. J Pharm Pharmaceut Sci. 1998; 1, 66-73.
- Maurya S. K., Bali V., Pathak K. Bilayered transmucosal drug delivery system of pravastatin sodium: Statistical optimization, in vitro, ex vivo, in vivo and stability assessment. Drug Delivery. 2012; 19, 45-57.
Go to original source...
Go to PubMed...
- Vasantha P. V., Puratchikody A., Mathew S. T., Balaraman A. K. Development and characterization of Eudragit based mucoadhesive buccal patches of salbutamol sulfate. Saudi Pharmaceutical Journal. 2011; 19, 207-214.
Go to original source...
Go to PubMed...
- Palem C. R., Gannu R., Doodipala N., Yamsani V. V., Yamsani M. R. Transmucosal Delivery of Domperidone from Bilayered Buccal Patches: In Vitro, Ex Vivo and In Vivo Characterization. Arch Pharm Res. 2011; 34, 1701-1710.
Go to original source...
Go to PubMed...
- Saranjit Singh. Drug stability testing and shelf-life determination according to international guidelines. Pharmaceutical technology. 1999; 23, 68-88.
- Chang H. S., Park H., Robinson J. R. Bioadhesive polymers as platform for oral controlled drug delivery: II, synthesis and evaluation of some swelling, water insoluble bioadhesive polymers. J. Pharm. Sci. 1985; 74, 399-405.
Go to original source...
Go to PubMed...
- Park H., Robinson J. R. Physico chemical properties of water insoluble polymers important to mucin epithelial adhesion. J. Control. Rel. 1985; 2, 47-57.
Go to original source...
- Shidhaye S. S., Saindane N. S., Sutar S., Kadam V. Mucoadhesive Bilayered Patches for Administration of Sumatriptan Succinate. AAPS PharmSciTech. 2008; 9, 1-8.
Go to original source...
Go to PubMed...
- Sakellariou P. A study of the leaching/retention of watersoluble polymers in blends with ethylcellulose using torsional braid analysis. J. Control. Rel. 1998; 7, 147-157.
Go to original source...
- Nappinnai M., Chandanbala R., Balaijirajan R. Formulation and Evaluation of Nitrendipine Buccal Films. Indian J Pharm Sci. 2008; 70, 631-635.
Go to original source...
Go to PubMed...
- Satishbabu B. K., Srinivasan B. P. Preparation and Evaluation of Buccoadhesive Films of Atenolol. Indian J Pharm Sci. 2008; 70, 175-179.
Go to original source...
Go to PubMed...
- Hao J. S., Chan L. W., Shen Z. X., Heng P. W. Complexation between PVP and Gantrez polymer and its effect on release and bioadhesive properties of the composite PVP/Gantrez films. Pharm Dev Technol. 2004; 9, 379-386.
Go to original source...
Go to PubMed...
- Nafee N. A., Boraie N. A., Ismail F. A., Mortada L. M. Mucoadhesive buccal patches of miconazole nitrate: in vitro/in vivo performance and effect of ageing. Int J Pharm. 2003; 264, 1-14.
Go to original source...
Go to PubMed...
- Patel V. M., Prajapati B. G., Patel M. M. Effect of hydrophilic polymers on buccoadhesive eudragit patches of Propranolol hydrochloride using factorial design. AAPS PharmSciTech. 2007; 8 (2) Article 45. http://www.aapspharmscitech.org.
Go to original source...
Go to PubMed...
- Chary C. B., Vani G., Rao Y. M. In vitro and in vivo adhesion testing of mucoadhesive drug delivery systems. Drug Dev Ind Pharm. 1999; 25, 685-690.
Go to original source...
Go to PubMed...
- Yehia S. A., El Gazayerly O. N., Basalious E. B. Fluconazole Mucoadhesive Buccal Films: In vitro/In Vivo Performance. Curr Drug Deliv. 2009; 6, 17-27.
Go to original source...
Go to PubMed...
- Lee H. Y., Wu P. C., Lee Y. J. Stab: An R package for drug stability data analysis. Compu methods and programs in biomed. 2010; 100, 140-148.
Go to original source...
Go to PubMed...