Generic placeholder image

Infectious Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5265
ISSN (Online): 2212-3989

Research Article

Application of SRMS 154 as Sustained Release Matrix for the Delivery of Stavudine: In vitro and in vivo Evaluation and Effect of Poloxamer 188 on the Properties of the Tablets

Author(s): S.A. Chime*, A.A. Attama and G.C. Onunkwo

Volume 20, Issue 1, 2020

Page: [76 - 87] Pages: 12

DOI: 10.2174/1871526519666190313162635

Price: $65

Abstract

Background: Stavudine is an antiretroviral therapy with so many side effects and has a short half-life of 1.5 h. It degrades to thymine under hydrolytic, oxidative and photolytic conditions hence has major formulation challenges.

Objectives: To formulate sustained release lipid based stavudine and to study the properties of the formulations by in vitro and in vivo methods.

Methods: Stavudine tablets were formulated by moulding using validated tablets moulds. The carrier used were solidified reverse micellar solution (SRMS) made up of varying ratios of hydrogenated palm oil and Phospholipid admixtures. Evaluation tests were carried out on the tablets using both Pharmacopoeial and non Pharmacopoeial test. Drug release was studied in both simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.2). In vivo release was studied using Wistar rats.

Results: The results showed that stavudine tablets exhibited weight range of 372 ± 0.14 to 386 ± 0.52 mg, friability ranged from 0.00 to 0.13 % and hardness ranged from 4.27 ± 0.25 to 5.30 ± 0.21 Kgf. Tablets formulated with SRMS 1:2 had erosion time range of 60.80 ± 1.23 to 87.90 ± 2.33 min and was affected significantly by the presence of Poloxamer 188 (p < 0.05). The formulations exhibited T100 % at 10 to13 h in SIF. Stavudine tablets showed the area under the curve (AUC) of 854.0 μg/h/ml, significantly higher than the AUC of the reference (p < 0.05).

Conclusion: Stavudine SRMS-based tablets had good stability and sustained release properties. Formulations containing 1 % Poloxamer 188 exhibited enhanced in vivo absorption and hence could be used once daily in order to enhance the bioavailability of this drug.

Keywords: HIV, Tablets, Lipids, Area under the curve, Stavudine, Solidified reverse micelles.

Graphical Abstract
[1]
Dhirendra, K.; Vivek, D.; Shaila, L.; Brajesh, P. Design and evaluation of sustained-release matrix once daily formulation of stavudine. Int. J. Drug Deliv., 2010, 2, 125-134.
[http://dx.doi.org/10.5138/ijdd.2010.0975.0215.02021]
[2]
McCormick, D. Evolution in direct compression. Pharm. Technol., 2005, 29, 52-62.
[3]
Onyechi, J.O.; Chime, S.A.; Onyishi, I.V. Formulation and evaluation of Allium Sativum tablets for improved oral delivery. Int. J. Pharm. Sci. Rev. Res., 2013, 22(1), 6-10.
[4]
Chime, S.A.; Onyishi, I.V.; Onyechi, J.O. Co-processed metronidazole granules for tabletting: Formulation and in vitro evaluation. Int. J. Pharm. Sci. Rev. Res., 2013, 22(2), 13-17.
[5]
Agarwal, G.; Agarwal, S.; Karar, P.K. Oral sustained release tablets: An overview with a special emphasis on matrix tablet. Amer J Adv Drug Del, 2017, 5(2), 64-76.
[6]
Germershaus, O.; Lühmann, T.; Rybak, J.C. Application of natural and semi-synthetic polymers for the delivery of sensitive drugs. Int. Mater. Rev., 2015, 60(2), 101-131.
[http://dx.doi.org/10.1179/1743280414Y.0000000045]
[7]
Onyishi, I.V.; Chime, S.A.; Okoroji, C.A. Physicochemical properties of microcrystalline cellulose from Saccharum officinarum: Comparative evaluation with Avicel® pH 101. Amer J PharmTech Res, 2013, 3(5), 414-426.
[8]
Reithmeier, H.J. Herrmann and Gopferich A. Development and characterisation of lipid microparticles as a drug carrier for somatostatin. Int. J. Pharm., 2001, 218, 133-143.
[http://dx.doi.org/10.1016/S0378-5173(01)00620-2] [PMID: 11337157]
[9]
Ravi Kumar, M.N. Nano and microparticles as controlled drug delivery devices. J. Pharm. Pharm. Sci., 2000, 3(2), 234-258.
[PMID: 10994037]
[10]
Onyishi, I.V.; Chime, S.A.; Echezona, O.O. Formulation of novel sustained release rifampicin-loaded solid lipid microparticles based on structured lipid matrices from Moringa oleifera; Pharm Dev Tech, 2014, pp. 1-9.
[http://dx.doi.org/10.3109/10837450.2014.898654.]
[11]
Attama, A.A.; Schicke, B.C.; Müller-Goymann, C.C. Further characterization of theobroma oil-beeswax admixtures as lipid matrices for improved drug delivery systems. Eur. J. Pharm. Biopharm., 2006, 64(3), 294-306.
[http://dx.doi.org/10.1016/j.ejpb.2006.06.010] [PMID: 16949805]
[12]
Attama, A.A.; Müller-Goymann, C.C. A critical study of novel physically structured lipid matrices composed of a homolipid from Capra hircus and theobroma oil. Int. J. Pharm., 2006, 322(1-2), 67-78.
[http://dx.doi.org/10.1016/j.ijpharm.2006.05.044] [PMID: 16828247]
[13]
Attama, A.A.; Müller-Goymann, C.C. Investigation of surface-modified solid lipid nanocontainers formulated with a heterolipid-templated homolipid. Int. J. Pharm., 2007, 334(1-2), 179-189.
[http://dx.doi.org/10.1016/j.ijpharm.2006.10.032] [PMID: 17140752]
[14]
Attama, A.A.; Nkemnele, M.O. In vitro evaluation of drug release from self micro-emulsifying drug delivery systems using a biodegradable homolipid from Capra hircus. Int. J. Pharm., 2005, 304(1-2), 4-10.
[http://dx.doi.org/10.1016/j.ijpharm.2005.08.018] [PMID: 16198521]
[15]
Attama, A.A.; Okafor, C.E.; Builders, P.F.; Okorie, O. Formulation and in vitro evaluation of a PEGylated microscopic lipospheres delivery system for ceftriaxone sodium. Drug Deliv., 2009, 16(8), 448-457.
[http://dx.doi.org/10.3109/10717540903334959] [PMID: 19839789]
[16]
Friedrich, I.; Müller-Goymann, C.C. Characterization of solidified reverse micellar solutions (SRMS) and production development of SRMS-based nanosuspensions. Eur. J. Pharm. Biopharm., 2003, 56(1), 111-119.
[http://dx.doi.org/10.1016/S0939-6411(03)00043-2] [PMID: 12837489]
[17]
Obitte, N.C.; Chime, S.A.; Magaret, A.A. Some in vitro and pharmacodynamic evaluation of indomethacin solid lipid microparticles. Afr. J. Pharm. Pharmacol., 2012, 6(30), 2309-2317.
[http://dx.doi.org/10.5897/AJPP12.524]
[18]
Brown, S.A.; Chime, S.A.; Attama, A.A. In vitro and in vivo characterisation of piroxicam-loaded dika wax lipospheres. Trop. J. Pharm. Res., 2013, 12(1), 33-38.
[http://dx.doi.org/10.4314/tjpr.v12i1.6]
[19]
Gao, P.; Guyton, M.E.; Huang, T.; Bauer, J.M.; Stefanski, K.J.; Lu, Q. Enhanced oral bioavailability of a poorly water soluble drug PNU-91325 by supersaturatable formulations. Drug Dev. Ind. Pharm., 2004, 30(2), 221-229.
[http://dx.doi.org/10.1081/DDC-120028718] [PMID: 15089057]
[20]
Sarkar, N.N. Mifepristone: bioavailability, pharmacokinetics and use-effectiveness. Eur. J. Obstet. Gynecol. Reprod. Biol., 2002, 101(2), 113-120.
[http://dx.doi.org/10.1016/S0301-2115(01)00522-X] [PMID: 11858883]
[21]
Chime, S.A.; Attama, A.A.; Builders, P.F.; Onunkwo, G.C. Sustained-release diclofenac potassium-loaded solid lipid microparticle based on solidified reverse micellar solution: in vitro and in vivo evaluation. J. Microencapsul., 2013, 30(4), 335-345.
[http://dx.doi.org/10.3109/02652048.2012.726284] [PMID: 23057661]
[22]
Schneeweis, A.; Müller-Goymann, C.C. Controlled release of solid-reversed-micellar-solution (SRMS) suppositories containing metoclopramide-HCl. Int. J. Pharm., 2000, 196(2), 193-196.
[http://dx.doi.org/10.1016/S0378-5173(99)00419-6] [PMID: 10699716]
[23]
Sweetman, S.C. Martindale. In: The complete reference, 33rd ed; Pharmaceutical Press: London, 2002; p. 641.
[24]
Dunge, A.; Chakraborti, A.K.; Singh, S. Mechanistic explanation to the variable degradation behaviour of stavudine and zidovudine under hydrolytic, oxidative and photolytic conditions. J. Pharm. Biomed. Anal., 2004, 35(4), 965-970.
[http://dx.doi.org/10.1016/j.jpba.2004.03.007] [PMID: 15193743]
[25]
European Pharmacopoeia; Council of Europe: Strasbourg, 2005, pp. 225-258.
[26]
British Pharmacopoeia. British Pharmacopoeia; Her Majesty’s Stationery Office: London, 2009, Vol. III, pp. 6578-6585.
[27]
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.
[http://dx.doi.org/10.1002/jps.2600521210] [PMID: 14088963]
[28]
Ritger, P.L.; Peppas, N.A. A simple equation for description of solute release 1. Fickian and non-Fickian release from non swellable device in the form of slabs, spheres, cylinders and discs. J. Control. Release, 1987, 5, 23-36.
[http://dx.doi.org/10.1016/0168-3659(87)90034-4]
[29]
Kamal, A.H.; Samah, F.; Hammad, S.F. A review on uv spectrophotometric methods for simultaneous multicomponent analysis. Eur. J. Pharm. Med. Res., 2016, 3(2), 348-360.
[30]
Chime, S.A.; Onunkwo, G.C.; Onyishi, I.V. Kinetics and mechanisms of drug release from swellable and non swellable matrices: a review. Res. J. Pharm. Biol. Chem. Sci., 2013, 4, 97-103.
[31]
Bouwstra, J.A.; Gooris, G.S.; Salomons-de Vries, M.A. Structure of human stratum corneum as a function of temperature and hydration: A wide-angle X-ray diffraction study. Int. J. Pharm., 1992, 84, 205-216.
[http://dx.doi.org/10.1016/0378-5173(92)90158-X]
[32]
Moghimi, H.R.; Williams, A.C.; Barry, B.W. A lamellar matrix model for stratum corneum intercellular lipids. I. Characterization and comparison with stratum corneum intercellular structure. Int. J. Pharm., 1996, 131, 103-115.
[http://dx.doi.org/10.1016/0378-5173(95)04306-3]
[33]
Chinaeke, E.E.; Chime, S.A.; Kenechukwu, F.C. Formulation of novel artesunate-loaded solid lipid microparticle (SLMs) based on dika wax matrices: In vitro and in vivo evaluation. J. Drug Deliv. Sci. Technol., 2014, 24(1), 1-9.
[http://dx.doi.org/10.1016/S1773-2247(14)50010-X]
[34]
Umeyor, E.C.; Kenechukwu, F.C.; Ogbonna, J.D.; Chime, S.A.; Attama, A. Preparation of novel solid lipid microparticles loaded with gentamicin and its evaluation in vitro and in vivo. J. Microencapsul., 2012, 29(3), 296-307.
[http://dx.doi.org/10.3109/02652048.2011.651495] [PMID: 22283701]
[35]
Gugu, T.H.; Chime, S.A.; Attama, A.A. Solid lipid microparticles: An approach for improving oral bioavailability of aspirin; Asian J Pharm Sci, 2015.
[36]
Kuentz, M. Lipid-based formulations for oral delivery of lipophilic drugs. Drug Discov. Today. Technol., 2012, 9(2), e71-e174.
[http://dx.doi.org/10.1016/j.ddtec.2012.03.002] [PMID: 24064269]
[37]
Pang, K.S.; Lichuan, L.; Huadong, S. Interaction of drug transporters with excipients. In role of lipid excipients in modifying oral and parenteral drug delivery; Wasan, K.M., Ed.; Wiley, John Wiley and Sons,, 2007, pp. 1-31.
[38]
Bogman, K.; Erne-Brand, F.; Alsenz, J.; Drewe, J. The role of surfactants in the reversal of active transport mediated by multidrug resistance proteins. J. Pharm. Sci., 2003, 92(6), 1250-1261.
[http://dx.doi.org/10.1002/jps.10395] [PMID: 12761814]
[39]
Aungst, B.J.; Saitoh, H.; Burcham, D.L. Enhancement of the intestinal absorption of peptides and non-peptides. J. Control. Release, 1996, 41, 19-31.
[http://dx.doi.org/10.1016/0168-3659(96)01353-3]
[40]
Fouad, E.A.; El-badry, M.; Mahrous, G. In vitro investigation for embedding dextromethorphan in lipids using spray drying. Digest J Nano Bio, 2011, 6(3), 1129-1139.
[41]
Umeyor, E.C.; Kenechukwu, F.C.; Ogbonna, J.D.N. Investigation of solidified reverse micellar systems as novel carriers for oral delivery of gentamicin. J. Pharm. Res., 2012, 4914-492.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy