Volume : 09, Issue : 10, October – 2022

Title:

01.FORMULATION DEVELOPMENT AND EVALUATION OF VALACYCLOVIR HYDROCHLORIDE SUSTAINED RELEASE MATRIX TABLETS

Authors :

B.Nagaraju*, B.Sowmya Mishra

Abstract :

The present work is aimed at preparing and evaluating sustained release (SR) matrix tablets of valacyclovir hydrochloride (VH) using different polymers ethylcellulose (EC), hydroxypropyl methylcellulose (HPMCK100, HPMCE4PREMIUM), polyvinylpyrrolidone (PVPK 90), xanthum gum (XG) and Sodium carboxy methyl cellulose (NaCMC). In addition, the effect of different diluents (Micro Crystalline Cellusose MCC, Lactose, Di Calcium Phosphate DCP) on drug release was evaluated considering the method of preparation. A total of 18 different formulations were formulated (F1- F18). The blend of all formulations was evaluated for various precompression parameters like angle of repose, bulk density, tapped density, compressibility index, Hausner’s ratio and were found to be satisfactory. The tablets were evaluated for various parameters like weight variation, thickness, hardness, friability, wetting time, water absorption ratio, disintegration time, content uniformity and in vitro drug release. The data was subjected to kinetic analysis and the mechanism of the release was established. The results demonstrated that combination of both hydrophobic and hydrophilic polymers could be successfully employed for formulating sustained release matrix tablets of valacyclovir hydrochloride. The formulation containing drug, polymer (EC) and DCP as a diluent extended the drug release for 22 to 24 hours (R2=0.9989) which was established by subjecting the invitro release data to peppas korsmeyer kinetic analysis. The drug release rate was good with the tablets containing hydrophobic ethylcellulose (EC) polymers compared to with that of hydrophilic polymers (HPMC K 100M and E 4 premium). Erosion was established to be the predominant mechanism of release.

Cite This Article:

Please cite this article in B.Nagaraju and B.Sowmya Mishra , Formulation Development And Evaluation Of Valacyclovir Hydrochloride Sustained Release Matrix Tablets., Indo Am. J. P. Sci, 2022; 09(10).

Number of Downloads : 10

References:

1. Abhilash AS, Jayaprakash S, Nagarajan M, Dhachinamoorthi D, Design and evaluation of timolol maleate ocuserts. Indian J Pharm Sci. 2005;67(3):311-314.
2. Agarwal SP, Vasudha S, Anitha P. Spectrophotometric determination of atenolol and timolol dosage forms via charge-transfer complexation. Indian J Pharm Sci,\99&;53-55.
3. Amelia A, Vikram K. Design and evaluation of matrix-based controlled release tablets of diclofenac sodium and chondriotin sulphate. AAPS PhramSciTech 2007;8(4):E88.
4. Atul K, Ashok KT, Narendra KJ, Subheet J. Formulation and in vitro in vivo evaluation of extended-release matrix tablet of zidovudine: Influence of combination of hydrophilic and hydrophobic matrix formers. AAPS Pharm Sci Tech. 2006;7(I):E1.
5. Basak SC, Jayakumar Reddy BM, Lucas Mani KP. Formulation and release behaviour of sustained release ambroxol hydrochloride HPMC matrix tablet. Indian J Pharm Sci. 2006;594-597.
6. BASF. Technical information for Kollidon® SR, BASF AG, Ludwigshafen/Rh., Germany, 1999.
7. Bhalla HL, Handa AK. Development and evaluation of controlled release tablets of carbamazepine. Indian Drugs, 1999;36(2):100-105.
8. Bolton S, Bon C. Pharmaceutical Statistics: Practical and Clinical Applications. Marcel Dekkers New York, 2004.
9. Bourne DW. Pharmacokinetics. In: Banker GS, Rhodes CT. eds. Modern Pharmaceutics. 4th ed. Marcel Dekker, New York, NY, pp. 2002;67-92.
10. Bramhanker DM, Jaiswal SB. Controlled release medications. In: Biopharmaceutics and Pharmacokinetics a treatise. Vallabh Prakashan. 1995;335-375.
11. Carmen AL, Haruviki H, Jose GA, Ramon MP, Consuelo S, Angel C. Soft contact
12. lenses capable of sustained delivery of timolol. J Pharm Sci, 2002;91 (10):2182-2192.
13. Chetoni P, Mariotti Bianchi L, Giannaccini B, Saettone MF, Conte U, Sangalli ME. Ocular mini-tablets for controlled release of timolol: evaluation in rabbits. J Ocul Pharmacol Then 1996;12(3):245-252.
14. Chien YW. Controlled and modulated-release drug delivery systems. In: Swarbrick J, Balyan JC. Encyclopedia of Pharmaceutical Technology, New York: Marcel Dekker. 1990;2S1-313.
15. Chien YW. Novel drug delivery systems. 2nd ed. New York, Marcel Dekker, Inc. 1992.
16. Colombo P, Bettini R, Catellani PL. Drug volume fraction profile in the gel phase and drug release kinetics in hydroxypropylmethylcellulose matrices containing a soluble drug. Eur J Pharm Sci. 1999;9:33-40.
17. Colombo P, Bettini R, Massimo G. Drug diffusion front movement is important in drug release control from swellable matrix tablets, J Pharm Sci 1995;84(8):991-997.
18. Colombo P, Bettini R, Santi P, Peppas NA. Swellable matrices for controlled drug delivery: gel-layer behaviour, mechanisms and optimal performance. Pharm Sci Technol Today 2000;3:198-204.
19. Colombo P. Swelling-controlled release in hydrogel matrices for oral route. Adv Drug Del Rev, 1993;11:37-57.
20. Desai SJ, Singh P, Simonelli AP, Higuchi WL Investigation of factors influencing release of solid drug dispersed in inert matrices. IV. Some studies involving the polyvinyl chloride matrix. J Pharm Sci. 1966;55:598-602.
21. Dimitrios GF, Joke AB. Iontophoretic enhancement of timolol across human dermatomcd skin in-vitro. J Drug Target. 2004;12(l):19-24.
22. Draganoiu E, Andheria M, Sakr A. Evaluation of the new polyvinylacetate/povidone excipient for matrix sustained release dosage forms. Pharm Ind 2001;(63):624-629.
23. Ebube NK, Hikal A, Wyandt CM, Beer DC, Miller LG, Jones AB. Sustained release of acetaminophen from heterogeneous matrix tablets, influence of polymer ratio, polymer loading and coactive on drug release. Pharm Dev Technol 1997;2:161-170.
24. Fincher JH. Particle size of drugs and its relation to absorption and activity. J Pharm Sci. 1968;57:1825-1835.
25. Ford J, Rubinstein M, Hogan J. Propranolol hydrochloride and aminophylline release from matrix tablet containing hydroxypropylmethylcellulose. Int J Pharm. 1985;24:339-350.
26. Gao P, Nixon P, Skoug J. Diffusion in HPMC gels. II. Prediction of drug release rates from Hydrophilic matrix extended-release dosage forms. Pharm Res. 1995;12:965-971.
27. Gregory EA, Loksidh DG, John MH, Ernest JL, Alice CM, Robert MN, Joseph PR, Connie JS. Sustained-release tablet comprising reboxetine. US Patent,,WO/2004/010998, 2004.
28. Government of India Ministry of Health and Family Welfare. The Pharmacopoeia of India. Delhi, India: Controller of Publication. 1996.
29. Hadjiioannou IP, Christian GD, Koupparis MA. Quantitative Calculations in Pharmaceutical Practice and Research. VCH Publishers Inc, New York, NY, pp. 1993;345-348,
30. Hamid AM, Harris MS, Jaweria T, Rabia IY. Once-daily tablet formulation and invitro release evaluation of cefpodoxime using hydroxypropylmethylcellulose. AAPS Pharm Sci Tech. 2006;7(3):E78.
31. Honglei Jian , Liwei Zhua, Weiming Zhang, Dafeng Sun, Jianxin Jiang, Galactomannan (from Gleditsia sinensis Lam.) and xanthan gum matrix tablets for
32. controlled delivery of theophylline: In vitro drug release and swelling behaviour,
33. Carbohydrate Polymers 87 (2012) 2176– 2182.
34. Higuchi T. Mechanism of sustained action medication, theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. 1963;52:1145-1149.
35. Hiremath PS, Saha RN. Oral controlled release formulations of rifampicin. Fart II: Effect of formulation variables and process parameters on in vitro release. DrugDeliv. 2008; 15(3); 159-168,
36. Hixson AW, Crowell JH. Dependence of reaction velocity upon surface and agitation, I-theoretical consideration. IndEng Chem. 1931;23:923-931.
37. Hoffman A. Pharmacodynamic aspects of sustained release preparations. Advance Drug Deliv Rev. 1998;33:185-199.
38. Jaber E, Naser T. Formulation of sustained-release lithium carbonate matrix tablets; influence of hydrophilic materials on the release rate and in vitro-in vivo evaluation. J Pharm Pharmaceut Sci. 2004;7(3);338-344.
39. Jaleh V, Naser T, Fatemeh K. Use of hydrophilic natural gums in formulation of sustained-release matrix tablets of tramadol hydrochloride. AAPS PharmSciTech. 2006;7(1);E24.
40. Jantzen GM, Robinson JR. Sustained and controlled drug delivery system. In; Banker G. Rhodes. Modem Pharmaceutics, 3rd ed, Marcel Dekker.l996;921-942.
41. Kiil S, Dam JK. Controlled drug delivery from swellable hydroxypropylmethylcellulose matrices; model-based analysis of observed radial front movements. J Control Release. 2003;90:1-21.
42. Kim H? Fassihi R. A new ternary polymeric matrix system for controlled drug delivery of highly soluble drugs: I. Diltiazem hydrochloride. Pharm Res. 1997; 14(10):1415-1421.
43. Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Machanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983;15:25-35.
44. Krishnan PN, Sangeetha S, Venkatesh DN, Saraswathi R. Development and in vitro evaluation of sustained release tablets of theophylline using tamarind seed polysaccharide as release retardant. Asian J Pharmaceutics. 2007; I(4):213-216.
45. Lachman L, Lieberman HA, Kanig JL. The Theory and Practice of Industrial Pharmacy. Philadelphia, PA: Lea and Febiger. 1987;317r318.
46. Leon Shargcl, Susanna Wu-Pong, Andrew BC Yu. Modified-release drug products. In: Applied Biopharmaceutics & Pharmacokinetics, 5th cd. 2004.
47. Liu Js Zhang F, McGinity JW, Properties of lipophilic matrix tablets containing phenylpropanolamine hydrochloride prepared by hot-melt extrusion. Eur J Pharm Biopharm. 2001;52:181-190.
48. Lopes CM, Lobo JMS, Costa P, Pinto JF. Directly compressed mini matrix tablets containing ibuprofen: preparation and evaluation of sustained release. Drug Dev IndPharm. 2006;32:95-106.
49. Maggi L, Brum R, Conte U. High molecular weight polyethylene oxides (PEOs) as an alternative to HPMC in controlled release dosage forms. Int J Pharm. 2000; 195(l-2):229-238.
50. Mandana A, John C, Sunil JV, Paul MF, Russell PV, Amir R. Sustained release delivery of highly water-soluble compounds. US Patent., WO/2000/025757, 2000.
51. Manthena VS, Aditya M, Alka G, Sanjay G. Factors affecting mechanism and kinetics of drug release from matrix-based oral controlled drug delivery systems. AmJDrugDeliv. 2004;2(l):43-57.
52. Mockel JE, Lippoid BC. Zero order release from hydrocolloid matrices. Pharm Res. 1993;10:1066-1070.
53. Mulye NV, Turco SJ. A simple model based on first order kinetics to explain release of highly water soluble drugs from porous dicalcium phosphate dehydrate matrices. Drug Dev Ind Pharm. 1995;21:943-953.
54. Nair A, Gupta R, Vasanthi S, In vitro controlled release of alfuzosin hydrochloride using FIPMC-based matrix tablets and its comparison with marketed product. Pharm Dev Techno/. 2007;12(6):621-625.
55. Narasimhan B, Peppas NA. Molecular analysis of drug delivery systems controlled by dissolution of the polymer carrier. J Pharm Sci. 1997;86:297-304.
56. Nath BS, Venkatesh, Hiremath D. Formulation and evaluation of sustained release dosage form of theophylline using a combined hydrophobic and hydrophilic matrix. Indian J Pharm Sci. 2000; 62(l):33-36.
57. Nicholas G. Sustained release dosage forms. In: Leon Lachman, Herbert A.Liberman, Joseph LK. The Theory and Practice of Industrial Pharmacy, 3rd ed. Varghese Publishing House, Bombay, 1987;430-456.
58. Paul JS, Ryan TR, Ryan DM, Brent MB. Effects of lubricant level, method of mixing, and duration of mixing on a controlled-release matrix tablet containing hydroxypropylmethylcellulose. Drug Dev Ind Pharm. 1995;21 (19):2151 -2165.
59. Peppas NA. Analysis of fickian and non-fickian drug release from polymers. Pharm Acta Helv. 1985;60:110-111.
60. Pillay V, Fassihi R. Electrolyte-induced compositional heterogeneity:a novel approach for rate-controlled oral drug delivery. J Pharm Sci. 1999; 88(11):1140-1148.
61. B.Pradeep, M.Nagamadhu, David Banji, B. Bindu Madhavi, G. Arjun, K.Shekhar, Formulation and evaluation of valacyclovir hydrochloride microcapsules, International Journal of Pharmacy and Pharmaceutical Sciences Vol 3, Suppl 2, 2011
62. Raghuram RK, Srinivas M, Srinivas R. Once-daily sustained -release matrix tablets of nicorandil formulation and in vitro evaluation. AAPS PharmaSciTech. 2003;4(4):E61.
63. Raslan HK, Maswadeh. In vitro dissolution kinetic study of theophylline from mixed controlled release matrix tablets containing hydroxypropylmethylcellulose and glycerylbehenate. Indian J Pharm Sci. 2006;8:308-311.
64. Ravi PR, Kotreka UK, Saha RN. Controlled release matrix tablets of zidovudine: effect of formulation variables on the in vitro drug release kinetics. AAPS PharmSciTech 2008; 9(1):302-313.
65. Roberts M, Cespi M, Ford JL, Dyas AM, Downing J, Martini LG, Crowley PL Influence of ethanol on aspirin release from hypromellose matrices. Int J Pharm. 2007;332(l-2):31-37.
66. Robinson JR, Eriksen SP. Theoretical formulation of sustained-release dosage forms. J Pharm Sci. 1966;55:1254-1263.
67. Robinson JR, Lee VHL. Controlled Drug Delivery: Fundamentals and Applications.. 2nd ed. New York, Marcel Dekker, Inc. 1987.
68. Ruchatz F, Kolter K, Wittermer S. Kollidon*’ SR – a new excipient for
sustained release matrices. Proceed Int 7 Symp Control Pel Bioact Mater.
69. Controlled Release Society inc.,1999;26.
70. Saleh M, Al-Saidan, Krishnaiah YSR, Srinivas Patro S, Satyanarayana V. In vitro and in vivo evaluation of guar gum matrix tablets for oral controlled release of water-soluble diltiazem hydrochloride. AAPS PharmSciTech. 2005;6(1):E5.
71. Salsa T, Veiga F, Pina ME. Oral controlled-release dosage forms. I. Cellulose ether polymers in hydrophilic matrices. Drug Dev lnd Pharm. 1997;23:929-938.
72. Sandip BT, Krishna Murthy T, Raveendra Pai M, Pavak RM, Pasula BC. Controlled release formulation of tramadol hydrochloride using hydrophilic and hydrophobic matrix system. AAPS PharmSciTech. 2003;4(3):l-7.
73. Selim R, Mohiuddin AQ, Syed SH. Comparative evaluation of plastic, hydrophobic and hydrophilic polymers as matrices for controlled-release drug delivery. J Pharm Pharmaceut Set 2003;6(2):282-291.
74. Shruti Chopra, Gayathri VP, Sanjay KM. Release modulating hydrophilic matrix systems of losartan potassium: Optimization of formulation using statistical experimental design. Eur J Pharm Sci. 2007;66:73-82.
75. Siepmann J, Kranz H, Bodmeier R, Peppas NA. HPMC-matrices for controlled drug delivery: a new model combining diffusion, swelling, and dissolution mechanisms and predicting the release kinetics. Pharm Res. 1999;16:1748-1756.
76. Silvina AB, Maria CL, Claudio JS„ In-vitro studies of diclofenac sodium controlled-release from biopolymeric hydrophilic matrices. J Pharm Pharmaceut ScL 2002;5(3):213-219.
77. Sinju Engineer, Zezhi JS, Nouman AK. Temperature/Humidity sensitivity of sustained-release formulations containing kollidon® SR. Drug Dev lnd Pharm. 2004;30(10):1089-1094.
78. Thomson. Physician’s Desk Reference PDR®. 60th ed, pp. 2006;1891-1894.
79. United States Pharmacopoeia! Convention, United States Pharmacopoeia-27 andNational Formulary-22, Asian ed, Inc., Rockvillc, MD.2004.
80. Venkataraman S5 Davar N, Chester A, Kliene L. An overview of controlled-release systems. In: wise DL.ed, Handbook of Pharmaceutical Controlled Release Technology, Marcel Dekker. 2000.
81. Vidyadhara S, Rama Rao P, Prasad JA. Formulation and evaluation of propranolol hydrochloride oral controlled release matrix tablets. Indian J Pharm Sci. 2004;66(2):188-192.
82. Vora B, Khopade AJ, Jain VVD, Shelly, Jain NK. Targeted oral drug delivery. Indian Drugs 1996;33(8):365-373.