AIDS constitutes one of the most serious infectious diseases, representing a major public health priority. Efavirenz (EFV), one of the most widely used drugs for this pathology, belongs to the Class II of the Biopharmaceutics Classification System for drugs with very poor water solubility. To improve EFV’s dissolution profile, changes can be made to the physical properties of the drug that do not lead to any accompanying molecular modifications. Therefore, the study objective was to develop and characterize systems with efavirenz able to improve its dissolution, which were co-processed with sodium lauryl sulfate (SLS) and polyvinylpyrrolidone (PVP). The technique used was co-micronization. Three different drug:excipient ratios were tested for each of the two carriers. The drug dispersion dissolution results showed significant improvement for all the co-processed samples in comparison to non-processed material and corresponding physical mixtures. The dissolution profiles obtained for dispersion with co-micronized SLS samples proved superior to those of co-micronized PVP, with the proportion (1:0.25) proving the optimal mixture. The improvements may be explained by the hypothesis that formation of a hydrophilic layer on the surface of the micronized drug increases the wettability of the system formed, corroborated by characterization results indicating no loss of crystallinity and an absence of interaction at the molecular level.
References
[1]
Ojewole, E.; Mackraj, I.; Naidoo, P.; Govender, T. Exploring the use of novel drug delivery systems for antiretroviral drugs. Eur. J. Pharm. Biopharm. 2008, 70, 697–710, doi:10.1016/j.ejpb.2008.06.020.
[2]
Mishra, S.; Chaturvedi, D.; Srivastava, A.; Tandon, P.; Ayala, A.P.; Siesler, H.W. Quantum chemical and experimental studies on the structure and vibrational spectra of efavirenz. Vib Spectrosc. 2010, 53, 112–116, doi:10.1016/j.vibspec.2010.03.007.
[3]
Ribeiro, J.A.D.; Moreira de Campos, L.M.; Alves, R.J.; Lages, G.P.; Pianetti, G.A. Efavirenz related compounds preparation by hydrolysis procedure: Setting reference standards for chromatographic purity analysis. J. Pharm. Biomed. 2007, 43, 298–303, doi:10.1016/j.jpba.2006.06.010.
[4]
Madhavi, B.B.; Kusum, B.; Krishna Chatanya, C.H.; Madhu, M.N.; Sri Harsha, V.; Banji, D. Dissolution enhancement of efavirenz by solid dispersion and PEGylation techniques. Int. J. Pharm. Investig. 2011, 1, 29–34, doi:10.4103/2230-973X.76726.
[5]
Mahapatra, S.; Thakur, T.S.; Joseph, S.; Varughese, S.; Desiraju, G.R. New solid state forms of the anti-HIV drug efavirenz. Conformational flexibility and high Z’ issues. Cryst. Growth Des. 2010, 10, 3191–3202, doi:10.1021/cg100342k.
[6]
Rudnic, E.M.; Schwartz, J.B. Oral solid dosage forms. In Remington: The Science and Practice of Pharmacy, 21st; David, B.T., Ed.; Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2000; pp. 889–928.
[7]
Vogt, M.; Kunath, K.; Dressman, J.B. Dissolution enhancement of fenofibrate by micronization, cogrinding and spray-drying: Comparison with commercial preparations. Eur. J. Pharm. Biopharm. 2008, 68, 283–288, doi:10.1016/j.ejpb.2007.05.010.
[8]
Omelczuk, M.O.; Wang, C.C.; Pope, G. Influence of micronization on the compaction properties of an investigational drug using tableting index analysis. Eur. J. Pharm. Biopharm. 1996, 43, 95–100.
[9]
Kanig, J.; Lachman, L.; Lieberman, H. Teoria e Prática na Indústria Farmacêutica; Funda？？o Calouste Gulibenkian: Lisboa, Portugal, 2001; Volume 2.
[10]
Makhlof, A.; Miyazaki, Y.; Tozuka, Y.; Takeuchi, H. Cyclodextrins as stabilizers for the preparation of drug nanocrystals by the emulsion solvent diffusion method. Int. J. Pharm. 2008, 357, 280–285, doi:10.1016/j.ijpharm.2008.01.025.
[11]
Miyamoto, Y.; Nakahara, M.; Motoyama, K.; Ishiguro, T.; Oda, Y.; Yamanoi, T.; Okamoto, I.; Yagi, A.; Nishimura, H.; Hirayama, F.; et al. Improvement of some physicochemical properties of arundic acid, (R)-(？)-2-propyloctanonic acid, by complexation with hydrophilic cyclodextrins. Int. J. Pharm. 2011, 413, 63–72, doi:10.1016/j.ijpharm.2011.04.022.
[12]
Chiappetta, D.A.; Hocht, C.; Taira, C.; Sosnik, A. Efavirenz-loaded polymeric micelles for pediatric anti-HIV pharmacotherapy with significantly higher oral bioavailability. Nanomedicine 2010, 5, 11–23, doi:10.2217/nnm.09.90.
[13]
Chiappetta, D.A.; Hocht, C.; Taira, C.; Sosnik, A. Oral pharmacokinetics of the anti-HIV efavirenz encapsulated within polymeric micelles. Biomaterials 2011, 32, 2379–2387, doi:10.1016/j.biomaterials.2010.11.082.
[14]
Choi, K.C.; Bang, J.Y.; Kim, P.I.; Kim, C.; Song, C.E. Amphotericin B-incorporated polymeric micelles composed of poly (D,L-lactide-co-glycolide)/dextran graft copolymer. Int. J. Pharm. 2008, 355, 224–230, doi:10.1016/j.ijpharm.2007.12.011.
[15]
Francis, M.F.; Lavoie, L.; Winnik, F.M.; Leroux, J.C. Solubilization of cyclosporin A in dextran-g-polyethyleneglycolalkyl ether polymeric micelles. Eur. J. Pharm. Biopharm. 2003, 56, 337–346, doi:10.1016/S0939-6411(03)00111-5.
[16]
Richter, A.; Olbrich, C.; Krause, M.; Kissel, T. Solubilization of Sagopilone, a poorly water-soluble anticancer drug, using polymeric micelles for parenteral delivery. Int. J. Pharm. 2010, 389, 244–253, doi:10.1016/j.ijpharm.2010.01.032.
[17]
Shin, H.C.; Alani, A.W.G.; Rao, D.A.; Rockich, N.C.; Kwon, G.S. Multi-drug loaded polymeric micelles for simultaneous delivery of poorly soluble anticancer drugs. J. Control Release 2009, 140, 294–300, doi:10.1016/j.jconrel.2009.04.024.
[18]
Dolenc, A.; Kristl, J.; Baumgartner, S.; Planin？ek, O. Advantages of celecoxib nanosuspension formulation and transformation into tablets. Int. J. Pharm. 2009, 376, 204–212, doi:10.1016/j.ijpharm.2009.04.038.
[19]
Gao, L.; Liu, G.Y.; Wang, X.Q.; Liu, F.; Xu, Y.F.; Ma, J. Preparation of a chemically stable quercetin formulation using nanosuspension technology. Int. J. Pharm. 2011, 404, 231–237, doi:10.1016/j.ijpharm.2010.11.009.
[20]
Kayser, O.; Olbrich, C.; Yardley, V.; Kiderlen, A.F.; Croft, S.L. Formulation of amphotericin B as nanosuspension for oral administration. Int. J. Pharm. 2003, 254, 73–75, doi:10.1016/S0378-5173(02)00686-5.
[21]
Prabhu, S.; Ortega, M.; Ma, C. Novel lipid-based formulations enhancing the in vitro dissolution and permeability characteristics of a poorly water-soluble model drug, piroxicam. Int. J. Pharm. 2005, 301, 209–216, doi:10.1016/j.ijpharm.2005.05.032.
[22]
Destache, C.J.; Belgum, T.; Christensen, K.; Shibata, A.; Sharma, A.; Dash, A. Combination antiretroviral drugs in PLGA nanoparticle for HIV-1. BMC Infect. Dis. 2009, 198, doi:10.1186/1471-2334-9-198.
[23]
Yang, J.; Grey, K.; Doney, J. An improved kinetics approach to describe the physical stability of amorphous solid dispersions. Int. J. Pharm. 2010, 384, 24–31, doi:10.1016/j.ijpharm.2009.09.035.
[24]
Jain, R.A.; Brito, L.; Straub, J.A.; Tessier, T.; Bernstein, H. Effect of powder processing on performance of fenofibrate formulations. Eur. J. Pharm. Biopharm. 2008, 69, 727–734, doi:10.1016/j.ejpb.2007.12.006.
[25]
Shown, I.; Banerjee, S.; Ramchandran, A.V.; Geckeler, K.E.; Murthy, C.N. Synthesis of Cyclodextrin and Sugar-Based Oligomers for the Efavirenz Drug Delivery. Macromol. Symp. 2010, 287, 51–59, doi:10.1002/masy.201050108.
[26]
Tajber, L.; Corrigan, O.I.; Healy, A.M. Physicochemical evaluation of PVP–thiazide diuretic interactions in co-spray-dried composites—Analysis of glass transition composition relationships. Eur. J. Pharm. Sci. 2005, 24, 553–563, doi:10.1016/j.ejps.2005.01.007.
[27]
Al-Hamidi, H.; Edwards, A.A.; Mohammad, M.A.; Nokhodchi, A. Glucosamine HCl as a new carrier for improved dissolution behaviour: Effect of grinding. Colloid Surface B 2010, 81, 96–109, doi:10.1016/j.colsurfb.2010.06.028.
[28]
Barzegar-Jalali, M.; Valizadeh, H.; Shadbad, M.R.S.; Adibkia, K.; Mohammadi, G.; Farahani, A.; Arash, Z.; Nokhodchi, A. Cogrinding as an approach to enhance dissolution rate of a poorly water-soluble drug (gliclazide). Powder Tech. 2010, 197, 150–158, doi:10.1016/j.powtec.2009.09.008.
[29]
Brittain, H.G. X-ray diffraction of pharmaceutical materials. In Profiles of Drug Substances, Excipients and Related Methodology; Elsevier: Milford, UK, 2003; Volume 30, pp. 271–319.
[30]
Gibson, M. Pharmaceutical Preformulation and Formulation—A Practical Guide from Candidate Drug Selection to Commercial Dosage Form; Interpharm/CRC Press: New York, NY, USA, 2004; pp. 45–46.
[31]
Otsuka, M.; Ofusa, T.; Matsuda, Y. Dissolution improvement of water-insoluble glybuzole by co-grinding and co-melting with surfactants and their physicochemical properties. Colloid Surface B 1998, 10, 217–226, doi:10.1016/S0927-7765(97)00064-7.
[32]
Vogt, M.; Vertzoni, M.; Kunath, K.; Reppas, C.; Dressman, J.B. Cogrinding enhances the oral bioavailability of EMD 57033, a poorly water soluble drug, in dogs. Eur. J. Pharm. Biopharm. 2008, 68, 338–345, doi:10.1016/j.ejpb.2007.06.011.
[33]
Jagadish, B.; Yelchuri, R.; Bindu, K.; Tangi, H.; Maroju, S.; Rao, V.U. Enhanced Dissolution and Bioavailability of Raloxifene Hydrochloride by Co-grinding with Different Superdisintegrants. Chem. Pharm. Bull 2010, 58, 293–300, doi:10.1248/cpb.58.293.
[34]
Van den Mooter, G.; Augustijns, P.; Blaton, N.; Kinget, R. Physico-chemical characterization of solid dispersions of temazepam with polyethylene glycol 6000 and PVP K30. Int. J. Pharm. 1998, 164, 67–80, doi:10.1016/S0378-5173(97)00401-8.
[35]
Bahl, D.; Bogner, R.H. Amorphization Alone Does Not Account for the Enhancement of Solubility of Drug Co-ground with Silicate: The Case of Indomethacin. AAPS PharmSciTech 2008, 1, 146–153.
[36]
Devilliers, M.M. Influence of agglomeration of cohesive particles on the dissolution behaviour of furosemide powder. Int. J. Pharm. 1996, 136, 175–179, doi:10.1016/0378-5173(95)04380-2.
[37]
United States Pharmacopeia 2009. USP’s pending monographs guideline. Available online: http//www.usp.org (accessed on 27 October 2011).
[38]
Moore, J.W.; Flanner, H.H. Mathematical comparison of curves with an emphsis on in vitro dissolution profiles. Pharm. Technol. 1996, 20, 64–74.
