Surface Solid Dispersion: A Novel Method for improving in-vitro dissolution and in-vivo pharmacokinetics of Meclizine hydrochloride

Bhaskar Daravath

doi:10.5958/0974-360X.2021.00121.9

Research Journal of Pharmacy and Technology

ISSN

0974-360X (Online)
0974-3618 (Print)

Submit Article

Surface Solid Dispersion: A Novel Method for improving in-vitro dissolution and in-vivo pharmacokinetics of Meclizine hydrochloride

Author(s): Bhaskar Daravath

Email(s): bdaravat@gitam.edu

DOI: 10.5958/0974-360X.2021.00121.9

Address: Bhaskar Daravath*
Department of Pharmaceutics, GITAM School of Pharmacy, GITAM Deemed to be University, Hyderabad, Telangana, India-502329.
*Corresponding Author

Published In: Volume - 14, Issue - 2, Year - 2021

View HTML

View PDF

ABSTRACT:
The current work is aimed to evaluate the role of Gelucire on the solubility; in-vitro dissolution rate and oral bioavailability of a poorly water soluble drug meclizine hydrochloride (MZ). Polyethylene glycol 8000, Gelucire 50/13 and Gelucire 44/14 solid dispersions with surface adsorbents (SSDs) and physical mixtures were prepared using MZ as a model drug. Interaction between carrier and drug, solid state characterization of drug in formulations as well as in physical mixtures was studied using FTIR, DSC and XRD. The effect of Gelucire on solubility and dissolution of MZ was studied through in-vitro dissolution studies. The results indicated that no interactions between Gelucire and drug. Solid state characterization showed reduction in crystallinity that further supports increment in solubility and dissolution. The presence of Gelucire 44/14 in the formulation showed significant enhancement in solubility (152 folds) and dissolution rate (7.23 folds). In vivo bioavailability studies indicated significant (p<0.05) increase in AUC (5497.76±67.83ng-h/ml) with higher Cmax (791.10±40.04 ng/ml) and faster onset of action of MZ from the formulation containing Gelucire 44/14. In vivo pharmacokinetic studies showed optimised formulation was 209 % relatively bioavailable compared with MZ pure drug. The results suggest that Gelucire can be useful in delivering poorly soluble drug such as meclizine hydrochloride with improved solubility, dissolution and bioavailability.

Keywords:

Cite this article:
Bhaskar Daravath. Surface Solid Dispersion: A Novel Method for improving in-vitro dissolution and in-vivo pharmacokinetics of Meclizine hydrochloride. Research J. Pharm. and Tech. 2021; 14(2):685-693. doi: 10.5958/0974-360X.2021.00121.9

Cite(Electronic):
Bhaskar Daravath. Surface Solid Dispersion: A Novel Method for improving in-vitro dissolution and in-vivo pharmacokinetics of Meclizine hydrochloride. Research J. Pharm. and Tech. 2021; 14(2):685-693. doi: 10.5958/0974-360X.2021.00121.9 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2021-14-2-17

REFERENCES:
1.   Chambin O, Jannin V. Interest of Multifunctional Lipid Excipients: Case of Gelucire® 44/14. Drug Dev Ind Pharm. 2005; 31(6): 527-534.
2.   da Fonseca Antunes AB, De Geest BG, Vervaet C, Remon JP. Gelucire 44/14 based immediate release formulations for poorly water-soluble drugs. Drug Dev Ind Pharm. 2013; 39(5): 791-8.
3.   Alladi S, Shastri NR. Semi solid matrix formulations of meloxicam and tenoxicam: an in vitro and in vivo evaluation. Arch. Pharm. Res. 2015; 38(5): 801–812
4.   Dordunoo SK, Ford JL, Rubinstein MH. Preformulation studies on solid dispersions containing triamterene or temazepam in polyethylene glycols or Gelucire 44/14 for liquid filling of hard gelatin capsules. Drug Dev Ind Pharm. 1991; 17(12): 1685– 1713.
5.   Harikrishnan V, Sreejith M, Elthose MJ, Akash M. Gelucire: An Optional Innovative Tool for both Sustained and Fast Release of Drugs in Treating Diabetes Mellitus Type II Disease. Asian J. Res. Pharm. Sci. 2017; 7(1): 33-37.
6.   Shimpi S, Chauhan B, Mahadik KR, Paradkar A. Preparation and evaluation of diltiazem hydrochloride-Gelucire 43/01 floating granules prepared by melt granulation. AAPS Pharm Sci Tech. 2004; 5(3): 51–56.
7.   Kallakunta VR, Eedara BB, Jukanti R, Ajmeera RK, Bandari S. A Gelucire 44/14 and labrasol based solid self emulsifying drug delivery system: formulation and evaluation. J Pharm Invest. 2013; 43(3): 185-196.
8.   Srikanth MV, Murali GV, Sunil SA, Sreenivasa N, Praveen K, Ramana KV. Studies on the effect of hydrophilic carriers in the dissolution rate enhancement of poorly soluble drug, Bicalutamide. Research J. Pharm. and Tech. 2010;3(2):592-595.
9.   Kawakami K, Miyoshi K, Ida Y. Solubilization behavior of poorly soluble drugs with combined use of Gelucire 44/14 and cosolvent. J Pharm Sci. 2004; 93(6): 1471–1479.
10.   Mohamed AA, Shalam MH. Enhancement of dissolution and in vivo evaluation of lornoxicam ternary system with Gelucire 50/13 and polysorbate 80. Research J. Pharm. and Tech. 2016; 9(2):121-127.
11.   Daravath B, Tadikonda RR, Vemula SK. Formulation and pharmacokinetics of gelucire solid dispersions of flurbiprofen. Drug Dev Ind Pharm.2015; 41(8): 1254-1262.
12.   Nidhi M, Shikha S. Characterization and solubility enhancement of etoricoxib in solid dispersion systems using lipid carriers Gelucire 44/14. Research J. Pharm. and Tech. 2010;3(2):578-582.
13.   Sheen PC, Kim SI, Petillo JJ, Serajuddin AT, Bio- availability of a poorly water-soluble drug from tablet and solid dispersions in humans, J. Pharm. Sci. 1991; 80(7): 712– 714.
14.   Wang Z, Lee B, Pearce D, Qian S, Wang Y, Zhang Q, Chow MS. Meclizine metabolism and pharmacokinetics: formulation on its absorption, J Clin Pharmacol. 2012; 52(9): 1343-1349.
15.   George SJ, Vasudevan DT. Studies on the Preparation, Characterization, and Solubility of 2-HP-β-Cyclodextrin-Meclizine HCl Inclusion Complexes, J Young Pharm. 2012; 4(4) 220-227.
16.   Patel PN, Ambizas EM. Meclizine: Safety and Efficacy in the Treatment and Prevention of Motion Sickness. Clinical Medicine Insights: Therapeutics. 2011; 3: 179-183.
17.   Chovan JP, Klett RP, Rakieten N, Comparison of Meclizine Levels in the Plasma of Rats and Dogs after Intranasal, Intravenous, and Oral Administration, J Pharm Sci. 1985; 74(10): 1111-1113.
18.   Takeuchi H, Nagira S, Yamamoto H, Kawashima Y. Solid dispersion particles of tolbutamide prepared with fine silica particles by the spray-drying method. Powder Technol. 2004;141(3):187–95.
19.   Tran HT, Park JB, Hong KH, Choi HG, Han HK, Lee J et al. Preparation and characterization of pH-independent sustained release tablet containing solid dispersion granules of a poorly water-soluble drug. Int J Pharm. 2011;415(1):83–88.
20.   Chauhan B, Shimpi S, Paradkar A. Preparation and evaluation of glibenclamide polyglycolized glycerides solid dispersions with silicon dioxide by spray drying technique. Eur J Pharm Sci. 2005; 26(2):219–30.
21.   Gupta MK, Goldman D, Bogner RH, Tseng YC. Enhanced drug dissolution and bulk properties of solid dispersions granulated with a surface adsorbent, Pharm Dev Technol. 2001; 6(4):563–72.
22.   Patel B, Parikh RH, Swarnkar D. Enhancement of dissolution of telmisartan through use of solid dispersion technique surface solid dispersion. J Pharm Bioall Sci 2012; 4: 64-8.
23.   Williams AC, Timmins P, Lu M, Forbes M. Disorder and dissolution enhancement: Deposition of ibuprofen on to insoluble polymers. Eur J Pharm Sci. 2005; 26(3):288-94.
24.   Rao M, Mandage Y, Thanki K, Bhise S. Dissolution improvement of simvastatin by surface solid dispersion technology. Dissolut Technol. 2010;17(2):27-34.
25.   Chowdary KPR, Rao SKS. Investigation of dissolution enhancement of itraconazole by solid dispersion in superdisintegrants. Drug Dev. Ind. Pharm. 2000;26(1):1207-11.
26.   Sharma S, Sher P, Badve S, Pawar AP. Adsorption of meloxicam on porous calcium silicate: Characterization and tablet formulation. AAPS Pharm Sci Tech. 2005;6(4): E618-E625.
27.   Barzegar JM, Maleki N, Garjani A, Khandar AA, Hosseinloo HM, Jabbari R. Enhancement of dissolution rate and anti-infammatory effects of piroxicam using solvent deposition technique. Drug Dev Ind Pharm. 2002;28(6):681-86.
28.   Derle DV, Pawar A, Patel JS, Rathi MN, Kothawade PI. Solubility enhancement of aceclofenac by solvent deposition method. Int. J. Pharm. Tech. Res. 2010;2(1):843-46.
29.   Smita K, Praveen C, Dhananjay M. Formulation and evaluation of solid dispersion by novel technique. Asian J. Res. Pharm. Sci. 2013;3(4):206-214.
30.   Shinkar DM, Patil AN, Saudagar RB. Solubility and dissolution enhancement of sulfasalazine by solid dispersion technique. Research J. Pharm. and Tech 2018; 11(4):1277-1282.
31.   Daravath B, Naveen CH, Vemula SK, Tadikonda RR. Solubility and dissolution enhancement of flurbiprofen solid dispersion using hydrophilic carriers. Braz. J. Pharm. Sci. 2017; 53(4): 1-10.
32.   Hajare AA, Shetty YT, Mali MN, Sarvagod SM. Characterization of melt (fusion) solid dispersions of nifedipine. Research J. Pharm. and Tech.2008;1(3):230-234.
33.   Daravath B and Tadikonda R. Formulation and evaluation of meclizine hydrochloride fast dissolving tablets using solid dispersion method. Asian J. Pharm. and Clin. Res. 2014; 7(2): 98-102.
34.   Chella N, Daravath B, Kumar D and Tadikonda R. Formulation and pharmacokinetic evaluation of polymeric dispersions containing valsartan. Eur J Drug Metab Pharmacokinet. 2016; 41(5): 517-26.
35.   Stippler E, Romero NE, Mauger JW. Formulating buffered dissolution media for sparingly soluble weak acid and weak base drug compounds based on microenvironmental pH considerations, Diss Tech. 2014; 21 (4): 20-25.
36.   Chella N, Tadikonda R. Melt dispersion granules: formulation and evaluation to improve oral delivery of poorly soluble drugs - a case study with valsartan. Drug Dev Ind Pharm. 2015; 41 (6): 888-897.
37.   Aaisha NS, Rukhsana AR, Anita SK, Indrajeet G, Dhananjay SS, Umair IS. Dissolution Enhancement of Ezetimibe by Solid Dispersion. Asian J. Research Chem. 2009; 2(3):325-331.
38.   Hanaa AF, Hammad MA, Nagia EM, Waleed B, Ahmed S. Modulation of clonazepam solubility using solid dispersion technique improves its solubility and bioavailability. Asian J. Research Chem. 2012;5(4):446-455.
39.   Smita K, Praveen C, Dhananjay M. Formulation development of solid dispersion prepared by newer approach: A Research. Asian J. Pharm. Res. 2013;3(4):172-180.
40.   Gaurav Tiwari, Ruchi Tiwari, Brijendra Srivastava, Awani K Rai. Development and optimization of multi-unit solid dispersion systems of poorly water soluble drug. Research J. Pharm. and Tech. 1(4): Oct.-Dec. 2008; Page 444-449.
41.   Mathews BR. Regulatory aspects of stability testing in Europe. Drug Dev Ind Pharm. 1999; 25 (7): 831–56.
42.   Mehatha AK, Suryadevara V, Lankapalli SR, Deshmukh AM, Sambath LP. Formulation and optimization of ezetimibe containing solid dispersions using kollidon VA64. Turk J Pharm Sci. 2014;11(2): 113-126.
43.   Daravath B, Tadikonda RR. Formulation and in vitro evaluation of flurbiprofen-polyethylene glycol 20000 solid dispersions. J App Pharm Sci. 2014; 4(7): 76-81.
44.   Foda NH, Jun HW, McCall JW. Quantitative Analysis of Meclizine in Tablet Formulations by HPLC. Anal Lett. 1988; 21 (7): 1177-1188.
45.   Bandari S, Jadav S, Eedara BB, Dhurke R, Jukanti R. Enhancement of Solubility and Dissolution Rate of Loratadine with Gelucire 50/13. J Pharm Inn. 2014; 9 (2): 141-149.
46.   Chauhan B, Shimpi S, Paradkar A. Preparation and evaluation of glibenclamide-polyglycolized glycerides solid dispersions with silicon dioxide by spray drying technique. Eur J Pharm Sci. 2005; 26 (2): 219-230.
47.   Bhaskar C, Shyam S, Anant P. Preparation and characterization of etoricoxib solid dispersions using lipid carriers by spray drying technique. AAPS Pharm Sci Tech; 2005; 6(3); E405-E412.
48.   El Bary AA, Louis D, Sayed S. Olmesartan medoxomil surface solid dispersion-based orodispersible tablets: formulation and in vitro characterization. J Drug Del Sci Tech. 2014; 24(6): 665-672.