The utility of self-emulsifying oil formulation to improve the poor solubility of the anti HIV drug CSIC

AIDS Research and Therapy

Nicholas C Obitte³  Lisa C Rohan²  Christianah M Adeyeye⁴  Michael A Parniak¹  Charles O Esimone⁵ 

[1] Department of Microbiology and Molecular Genetics, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

[2] Department of Pharmaceutical Sciences, School of Pharmacy, Magee Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA

[3] Department of Pharmaceutical Technology and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Nigeria

[4] Department of Biopharmaceutical Sciences, College of Pharmacy, Roosevelt University Schaumburg, Shaumburgh, IL, USA

[5] Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmaceutical Sciences, Nnamdi Azikiwe university, Awka, Anambra, Nigeria

关键词: Anhydrous emulsion;    Bioactivity;    CSIC;    Self-emulsification;    Poorly soluble;    Anti-HIV;   

Others  :  789591
DOI  :  10.1186/1742-6405-10-14

 received in 2012-09-25, accepted in 2013-05-23,  发布年份 2013

【 摘 要 】

Background

CSIC (5-chloro-3-phenylsulfonylindole-2-carboxamide), a non-nucleoside reverse transcriptase inhibitor (NNRTI) has not been advanced as a therapeutic anti-HIV candidate drug due to its low aqueous solubility and poor bioavailability.

Objective

The objective of this work was to formulate CSIC into self-emulsifying oil formulations for the purpose of improving its aqueous solubility and evaluating in vitro antiretroviral activity.

Methods

CSIC self-emulsifying oil formulations (SEFs) were formulated and evaluated for droplet size, zeta potential, polydispersity index (PDI), viscosity, emulsification time, stability and bioactivity.

Results

Results showed significantly improved solubility of CSIC in the SEFs.The concentration of co-surfactant affected the droplet size, zeta potential and polydispersity index. In vitro bioactivity studies showed that the CSIC SEFs retained full anti-HIV activity.

Conclusion

The in vitro data from this first attempt to formulate CSIC SEFs suggest that improvement on the aqueous solubility of CSIC through this delivery system may accentuate its antiretroviral effectiveness in vivo via bioavailability enhancement. The formulation is therefore intended as an oral anti-HIV agent for prophylactic and therapeutic uses.

【 授权许可】

   
2013 Obitte et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Tang B, Cheng G, Gu J, Xu C: Development of solid self-emulsifying drug delivery systems: preparation techniques and dosage forms. Drg Disc Tod 2008, 13:13-14.
• [2]Kommuru TR, Gurley B, Khan MA, Reddy IK: Self-emulsifyingdrug delivery systems (SEDDS) of coenzyme Q10: formulationdevelopment and bioavailability assessment. Int J Pharm 2001, 212:233-246.
• [3]Tang J, Sun J, He Z: Self-emulsifying drug delivery systems: Strategy for improving oral delivery of poorly soluble drugs. Curr Drg Ther 2007, 2:85-93.
• [4]Valizadeh H, Zakeri-Milani P, Barzegar-Jalali M, Mohammadi G, Danesh-Bahreini M, Adibkia K, Nokhodchi A: Preparation and characterization of solid dispersions of piroxicam with hydrophilic carriers. Drug Dev Ind Pharm 2007, 33(1):45-56.
• [5]Patel HM, Suhagia BN, Shah SA, Rathod IS, Parmar VK: Preparation and characterization of etoricoxib-b-cyclodextrin complexes prepared by the kneading method. Acta Pharm 2007, 57:351-359.
• [6]Che E, Zheng X, Sun C, Chang D, Jiang T, Wang S: Drug nanocrystals: a state of the art formulation strategy for preparing the poorly water-soluble drugs. Asian Journ Pharm Scs 2012, 7(2):85-95.
• [7]Joshi M, Pathak S, Sharma S, Patravale V: Solid microemulsion preconcentrate (NanOsorb) of artemether for effective treatment of malaria. Int J Pharm 2008, 362:172-178.
• [8]Watnasirichaikul S, Davies NM, Rades T, Tucker IG: Preparation of Biodegradable insulin nanocapsules from biocompatible microemulsions. Pharm Res 2000, 17:6.
• [9]Lawrence MJ, Rees GD: Microemulsion-based media as novel drug delivery systems. Adv Drug Deliv Rev 2000, 45:89-121.
• [10]Shafiq S, Faiyaz S, Sushma T, Farhan JA, Khar RK, Ali M: Development and bioavailability assessment of ramipril nanoemulsion formulation. Eur J Pharm Biopharm 2007, 66:227-243.
• [11]Talegaonkar S, Azeem A, Ahmad FJ, Khar RK, Pathan SA, Khan ZI: Microemulsions: a novel approach to enhanced drug delivery. Recent Pat Drug Deliv Formul 2008, 2:238-257.
• [12]Pouton CW, Porter JH: Formulation of lipid-based delivery systems for oral administration: materials, methods and strategies. Adv Drug Deliv Rev 2008, 60:625-637.
• [13]Sha X, Wu J, Chen Y, Fang X: Self-microemulsifying drug-delivery system for improved oral bioavailability of probucol: preparation and evaluation. Int Journ Nanomed 2012, 7:705-712.
• [14]Stegemanna S, Leveillerb F: When poor solubility becomes an issue: from early stage to proof of concept. Eur Journ Pharm Sci 2007, 31:249-261.
• [15]Motakis D, Parniak MA: A tight-binding mode of inhibition is essential for anti-human immunodeficiency virus type 1 virucidal activity of nonnucleoside reverse transcriptase inhibitors. Antim Agent Chem 2002, 6(46):1851-1856.
• [16]Hari BV, Dhevendaran K, Narayanan N: Development of Efavirenz nanoparticle for enhanced efficiency of anti-retroviral therapy against HIV and AIDS. BMC Infect Dis 2012, 12(Suppl 1):7.
• [17]Kasim NA, Whitehouse M, Ramachandran C, Bermejo M, Lennernaes H, Hussain AS, Junginger HE, Stavchansky SA, Midha KK, Shah VP: Molecular properties of WHO essential drugs and provisional biopharmaceutical classification. Mol Pharm 2004, 1:85-96.
• [18]Williams TM, Ciccaro TM, MacTough SC, Rooney CS, Balani SC, Condra JH, Emini EA, Goldman ME, Greenlee WJ, Kaufman LR: 5-Chloro-3- (phenylsulfonyl)indole-2-carboxamide: a novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase. J Med Chem 1993, 36:1291-1294.
• [19]Roehr B: Fashioning new tools to deter HIV transmission. J Int Assoc Phys AIDS Care 2000, 157-168.
• [20]Araya H, Tomita M, Hayashi M: The novel formulation design of self-emulsifying drug delivery systems (SEDDS) type o/w microemulsion 11: stable gastrointestinal absorption of a poorly water soluble new compound, ER-1258 in bile-fistula rats. Drug Metab Pharmacokinet 2005, 20(4):257-267.
• [21]Pouton CW: Formulation of poorly water-soluble drugs for oral administration: physicochemical and physiological issues and the lipid formulation classification system. Europ J Pharm Sci 2006, 29:278-287.
• [22]Yu LX, Amidon GL, Polli JE, Zhao H, Mehta MU, Conner DP, Shah VP, Lesko LJ, Chen ML, Lee VH: Biopharmaceutics classification system: the scientific basis for biowaiver extensions. Pharm Res 2002, 19:921-925.
• [23]Khoo SM, Humberstone AJ, Porter CJ, Edwards GA, Charman WN: Formulation design and bioavailability assessment of lipidicselfemulsifying formulations of halofantrine. Int J Pharm 1998, 167:155-164.
• [24]Munk C, Brandt SM, Lucero G, Landau NR: A dominant block to HIV-1 replication at reverse transcription in simian cells. Proc Natl Acad Sci USA 2002, 99(21):13843-13848.
• [25]Patel AR, Vavia PR: Preparation and in vivo evaluation of SMEDDS (Self-microemulsifying drug delivery system) containing fenofibrate. AAPS J 2007, 3:41.
• [26]Sinha S, Ali M, Baboota S, Ahuja A, Kumar A, Ali J: Solid dispersion as an approach for bioavailability enhancement of poorly water-soluble drug ritonavir. AAPS PharmSciTech 2010, 11(2):518-527.
• [27]Wilkinson JB, Moore RJ: Emulsions. In Harry’s cosmeticology. 7th edn, Burnt Mill Essex UK: George Godwin publishers, Longman House; 1982.
• [28]Hoar TP, Schulman JH: Transparent water-in-oil dispersions: the oleopathic hydro-micelle. Nature 1943, 152:102-103.
• [29]Patel MR, Patel RB, Parikh JR, Bhatt KK, Kundawala AJ: Microemulsions: as novel drug delivery vehicle. Latest Reviews 2007, 5:6.
• [30]Baboota S, Shakeel F, Ahuja A, Ali J, Shafiq S: Design, development and evaluation of novel nanoemulsion formulations for transdermal potential of celecoxib. Acta Pharm 2007, 57:315-332.
• [31]Kawakami K, Yoshikawa T, Moroto Y, Kanaoka E, Takahashi K, Nishihara Y, Masuda K: Microemulsion formulation for enhanced absorption of poorly soluble drugs, I. Prescription design. J Control Release 2002, 81:65-74.
• [32]Dixit AR, Rajput SJ, Patel SG: Preparation and bioavailability assessment of SMEDDS containing valsartan. AAPS Pharm Sci Tech 2010, 11(1):314-321.
• [33]Gershanik T, Benita S: Positively-charged self-emulsifying oil formulation for improving oral bioavailability of progesterone. Pharm Dev Technol 1996, 1:147-157.
• [34]Reiss H: Entropy-induced dispersion of bulk liquids. J Colloids Interface Sci 1975, 53:61-70.
• [35]Lam AC, Schechter RS: The theory of diffusion in microemulsions. J Colloid Interface Sci 1987, 120:56-63.
• [36]Hecqa J, Deleers M, Fanara D, Vranckx H, Amighi K: Preparation and characterization of nanocrystals for solubility and dissolution rate enhancement of nifedipine. Int J Pharm 2005, 299:167-177.