Design, Formulation and Evaluation of Physicochemical Properties of Valacyclovir Effervescent Tablet

Document Type : Original Article

Authors

1 School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

10.30476/tips.2022.95385.1145

Abstract

Valacyclovir (VA) displays antiviral activity against Herpes simplex virus (HSV) and Varicella zoster virus (VZV). The aim of this study was to design, formulate and evaluate the physicochemical properties of effervescent tablets containing VA in order to facilitate pill swallowing for the pediatric, elderly and bed-ridden patients. Sixteen formulations with different amounts of effervescent base were prepared by modified direct compression for the loading of 500 mg VA. The Design-Expert® software was then used to generate formulations using a full factorial design with four different variables: citric acid (A), sodium bicarbonate to citric acid molar ratio (B) 6000 (D). The prepared tablets were assessed for weight variation, hardness, thickness, friability, drug content, CO2 content, effervescence time and pH. To improve the taste of formulations, several sweeteners and fruity essences such as raspberry and cherries were used. F2 formulation was selected as the optimized formulation with the desirability of 72.8%. The optimized formulation had an effervescent time of 98.33±3.51 seconds, friability % of 0.55, pH value of 4.67±0.06, CO2 amount of 261.33 ± 20.26 mg and hardness of 77.23±3.12 N. It, therefore, seems that optimized effervescent tablets may be helpful for the delivery of VA in the treatment of herpes simplex or herpes zoster and chikenpox.
Keywords: Valacyclovir, Effervescent Tablet, Dry Granulation, Direct compression method.
Please cite this article as: Somayeh Taymouri, Abolfazl Mostafavi, Sajjad Zaretaghiabadi. Design, Formulation and Evaluation of Physicochemical Properties of Valacyclovir Effervescent Tablet. Trends in Pharmaceutical Sciences. 2022;8(3):135-146. doi: 10.30476/TIPS.2022.95385.1145.

Keywords


1.    Tekade B, Jadhao U, Thakare V, Bhortake  L. Formulation and evaluation of diclofenac sodium effervescent tablet. Infrared Spectroscopy. 2014;9(10):11.
2.    Rajlakshmi G, Vamsi C, Balchandar R, Damodharan N. Formulation and evaluation of effervescent tablets of diclofenac potassium. Int J Pharm Biomed Res. 2011;2:237-43. 
3.    Aslani A, Daliri A. Design, formulation and evaluation of its physicochemical properties of acetaminophen, ibuprofen and caffeine as effervescent tablet. J Rep Pharm Sci. 2016;5(2):122-4.
4.    Palanisamy P, Abhishekh R, Yoganand Kumar D. Formulation and evaluation of effervescent tablets of aceclofenac. Int Res J Pharm. 2011;2(12):185-90.
5.    Beutner KR. Valacyclovir: a review of its antiviral activity, pharmacokinetic properties, and clinical efficacy. Antiviral Res. 1995 Dec;28(4):281-90. doi: 10.1016/0166-3542(95)00066-6. PMID: 8669888.
6.    Vigil KJ, Chemaly RF. Valacyclovir: approved and off-label uses for the treatment of herpes virus infections in immunocompetent and immunocompromised adults. Expert Opin Pharmacother. 2010 Aug;11(11):1901-13. doi: 10.1517/14656566.2010.494179. PMID: 20536295.
7.    Kechagia IA, Kalantzi L, Dokoumetzidis A. Extrapolation of Valacyclovir Posology to Children Based on Pharmacokinetic Modeling. Pediatr Infect Dis J. 2015 Dec;34(12):1342-8. doi: 10.1097/INF.0000000000000910. PMID: 26379165.
8.    Azouz L, Dahmoune F, Rezgui F, G'Sell C. Full factorial design optimization of anti-inflammatory drug release by PCL-PEG-PCL microspheres. Mater Sci Eng C Mater Biol Appl. 2016 Jan 1;58:412-9. doi: 10.1016/j.msec.2015.08.058. Epub 2015 Sep 3. PMID: 26478328.
9.    The United States pharmacopeia 43. Na­tional formulary 38.Vol. 5. Rockville (MD): United States Pharmacopeial Convention, 2020.  p. 7993-7996 
10.    Taymouri S, Mostafavi A, Javanmardi M. Formulation and optimization of effervescent tablet containing bismuth sub-citrate. J Rep Pharm Sci. 2019;1;8(2):236-44. doi: 10.4103/jrptps.JRPTPS_11_19
11.    Fritz J, Streich WJ, Schwarm A, Clauss M. Condensing results of wet sieving analyses into a single data: a comparison of methods for particle size description. J Anim Physiol Anim Nutr (Berl). 2012 Oct;96(5):783-97. doi: 10.1111/j.1439-0396.2011.01183.x. Epub 2011 Jul 6. PMID: 21732992.
12.    The United States pharmacopeia 43. Na­tional formulary 38.Vol. 4. Rockville (MD): United States Pharmacopeial Convention, 2020.  p. 7183-7186
13.    Masareddy R, Yellanki SK, Patil BR, Manvi V. Development and evaluation of floating matrix tablets of riboflavin. Int J PharmTech Res. 2010 (2):1439-45. 
14.    The United States pharmacopeia 43. Na­tional formulary 38.Vol. 5. Rockville (MD): United States Pharmacopeial Convention, 2020.  p.8137-8138
15.    Patel SG, Siddaiah M. Formulation and evaluation of effervescent tablets: a review. J drug deliv ther. 2018;8:296-303. 
16.    Ozyurt H, Mehrad R. Development of effervescent tablet formulation which contain ferrous salt and ascorbic acid combination. EMU J Pharm Sci. 2019;3(1):35-49. 
17.    Thoke SB, Sharma YP, Rawat SS, Nangude SL. Formulation development & evaluation of effervescent tablet of Alendronate sodium with vitamin D3. J Drug Deliv Ther. 2013;3(5):65-74. 
18.    Aklima A, Baral P, Amin M, Emon T, Hossain M. Formulation and Quality Optimization of Effervescent Tablet of Glipizide: An Approach to Comfort Anti-Diabetic Medication. Mod Health Sci. 2020;3(2):14 
19.    Mahapatra AP, Saraswat R, Botre M, Paul B, Prasad N. Application of response surface methodology (RSM) in statistical optimization and pharmaceutical characterization of a patient compliance effervescent tablet formulation of an antiepileptic drug levetiracetam. Futur J Pharm Sci. 2020;6(1):1-4. 
20.    Yanze FM, Duru C, Jacob M. A process to produce effervescent tablets: fluidized bed dryer melt granulation. Drug Dev Ind Pharm. 2000 Nov;26(11):1167-76. doi: 10.1081/ddc-100100988. PMID: 11068690. 
21.    Rotthäuser B, Kraus G, Schmidt PC. Optimization of an effervescent tablet formulation containing spray dried L-leucine and polyethylene glycol 6000 as lubricants using a central composite design. Eur J Pharm Biopharm. 1998 Jul;46(1):85-94. doi: 10.1016/s0939-6411(97)00154-9. PMID: 9700026.
22.    Rani KC, Parfati N, Jayani NI, Kurniawan I, Kristiani NP. The Development of Moringa Leaves Effervescent Granules with Effervescent Agent of Citric Acid and Sodium Bicarbonate. Pharmaciana. 2021;11(2):225-40.