Top

AIDS Research and Therapy

Published in:

Open Access 01-12-2013 | Research

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

Authors: Nicholas C Obitte, Lisa C Rohan, Christianah M Adeyeye, Michael A Parniak, Charles O Esimone

Published in: AIDS Research and Therapy | Issue 1/2013

Abstract

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.

Available only for authorised users

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.

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. 10.1016/S0378-5173(00)00614-1CrossRefPubMed

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. 10.2174/157488507779422400.CrossRef

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. 10.1080/03639040600814965CrossRefPubMed

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.PubMed

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.

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. 10.1016/j.ijpharm.2008.06.012CrossRefPubMed

Watnasirichaikul S, Davies NM, Rades T, Tucker IG: Preparation of Biodegradable insulin nanocapsules from biocompatible microemulsions. Pharm Res. 2000, 17: 6-CrossRef

Lawrence MJ, Rees GD: Microemulsion-based media as novel drug delivery systems. Adv Drug Deliv Rev. 2000, 45: 89-121. 10.1016/S0169-409X(00)00103-4CrossRefPubMed

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. 10.1016/j.ejpb.2006.10.014CrossRefPubMed

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. 10.2174/187221108786241679CrossRefPubMed

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. 10.1016/j.addr.2007.10.010CrossRefPubMed

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. 10.2217/nnm.11.148.CrossRef

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. 10.1016/j.ejps.2007.05.110.CrossRef

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.CrossRef

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-CrossRef

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. 10.1021/mp034006hCrossRefPubMed

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. 10.1021/jm00061a022CrossRefPubMed

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. 10.2133/dmpk.20.257CrossRefPubMed

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. 10.1016/j.ejps.2006.04.016.CrossRef

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. 10.1023/A:1016473601633CrossRefPubMed

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. 10.1016/S0378-5173(98)00054-4.CrossRef

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. 10.1073/pnas.212400099PubMedCentralCrossRefPubMed

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. 10.1208/s12249-010-9404-1PubMedCentralCrossRefPubMed

27.

Wilkinson JB, Moore RJ: Emulsions. In Harry’s cosmeticology. 1982, 7th edn, Burnt Mill Essex UK: George Godwin publishers, Longman House,

28.

Hoar TP, Schulman JH: Transparent water-in-oil dispersions: the oleopathic hydro-micelle. Nature. 1943, 152: 102-103. 10.1038/152102a0.CrossRef

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.CrossRefPubMed

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. 10.1016/S0168-3659(02)00049-4CrossRefPubMed

32.

Dixit AR, Rajput SJ, Patel SG: Preparation and bioavailability assessment of SMEDDS containing valsartan. AAPS Pharm Sci Tech. 2010, 11 (1): 314-321. 10.1208/s12249-010-9385-0.CrossRef

33.

Gershanik T, Benita S: Positively-charged self-emulsifying oil formulation for improving oral bioavailability of progesterone. Pharm Dev Technol. 1996, 1: 147-157. 10.3109/10837459609029889CrossRefPubMed

34.

Reiss H: Entropy-induced dispersion of bulk liquids. J Colloids Interface Sci. 1975, 53: 61-70. 10.1016/0021-9797(75)90035-1.CrossRef

35.

Lam AC, Schechter RS: The theory of diffusion in microemulsions. J Colloid Interface Sci. 1987, 120: 56-63. 10.1016/0021-9797(87)90322-5.CrossRef

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. 10.1016/j.ijpharm.2005.05.014CrossRef

Title: The utility of self-emulsifying oil formulation to improve the poor solubility of the anti HIV drug CSIC
Authors: Nicholas C Obitte
Lisa C Rohan
Christianah M Adeyeye
Michael A Parniak
Charles O Esimone
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: AIDS Research and Therapy / Issue 1/2013
Electronic ISSN: 1742-6405
DOI: https://doi.org/10.1186/1742-6405-10-14

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Background

Objective

Methods

Results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Objective

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2013

Mutations in variable domains of the HIV-1 envelope gene can have a significant impact on maraviroc and vicriviroc resistance

Incidence and risk factors for first line anti retroviral treatment failure among Ugandan children attending an urban HIV clinic

Susac’s syndrome as HIV-associated immune reconstitution inflammatory syndrome

A new system for parallel drug screening against multiple-resistant HIV mutants based on lentiviral self-inactivating (SIN) vectors and multi-colour analyses

Increasing Hepatitis C treatment uptake among HIV-infected patients using an HIV primary care model

Virological failure of staggered and simultaneous treatment interruption in HIV patients who began Efavirenz-based regimens after allergic reactions to nevirapine

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page