A highly concentrated and taste-improved aqueous formulation of efavirenz for a more appropriate pediatric management of the anti-HIV therapy

Current HIV Research

Volumn 8, Issue 3, 2010, Pages 223-231

  Chiappetta, Diego A ^a,b   Hocht, Christian ^a   Sosnik, Alejandro ^a,b  

^a UNIVERSIDAD DE BUENOS AIRES   (Argentina)

^b National Science Research Council CONICET   (Argentina)

Author keywords

Efavirenz liquid formulation; In vitro drug delivery; Pediatric HIV; Physicochemical stability; Taste masking test

Indexed keywords

EFAVIRENZ; FLAVORING AGENT; SWEETENING AGENT; TRIACYLGLYCEROL; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; BENZOXAZINE DERIVATIVE;

AQUEOUS SOLUTION; ARTICLE; BURNING MOUTH SYNDROME; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG STABILITY; FLAVOR; HUMAN; HUMAN EXPERIMENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MUCOSA INFLAMMATION; NORMAL HUMAN; RANDOMIZED CONTROLLED TRIAL; SINGLE BLIND PROCEDURE; SOLUTION AND SOLUBILITY; SWALLOWING; TASTE; CHILD; DRUG DOSAGE FORM; DRUG STORAGE; ECONOMICS; PRESCHOOL CHILD;

ANTI-HIV AGENTS; BENZOXAZINES; CHILD; CHILD, PRESCHOOL; DOSAGE FORMS; DRUG STABILITY; DRUG STORAGE; HIV INFECTIONS; HUMANS; TASTE;

EID: 77954040160     PISSN: 1570162X     EISSN: None     Source Type: Journal    
DOI: 10.2174/157016210791111142     Document Type: Article

References (56)

1. AIDS epidemic update 2007, World health Organization. Available at: http://www.who.int/hiv/epiupdates/en/index.html (Accessed: 07/2009).
2. Panel of clinical practices for treatment of HIV infection, Guidelines for the use of antiretroviral agents to treat HIV infection in pediatric patients. Pan Am J Public Health 2001; 10: 426-35.
3. UNAIDS/WHO AIDS Epidemic. Available at: http://www.unaids.org/en/HIV (accesed 07/2009).
4. Shah CA. Adherence to high activity antiretroviral therapy (HAART) in pediatric patients infected with HIV: Issues and interventions. Indian J Pediatr 2007; 74: 55-60.
5. Andrews L, Friedland G. Progress in th HIV therapeutics and th challenges of adherence to antiretroviral therapy. Inf Dis Clin N Am 2000; 14: 1-26.
6. Medecins sans Frontieres, Press release, Available at: http://www.msf.org/ (accesed 07/2009).
7. The U.S. President's Emergency Plan for AIDS Relief (PEPFAR). Pediatric treatment and care. Available at: http://www.pepfar.gov/press/86524.htm (accesed 07/2009).
8. Giaquinto C, Morelli E, Fregonese F, et al. Current and future antiretroviral treatment options in paediatric HIV infection 1. Clin Drug Invest 2008; 28: 375-97.
9. Brown E. Antiretroviral therapy in children, HIV/AIDS primary care guide. Chapter 30, AIDS Education & Training Centers National Resource Center. 2007; pp. 419.
10. Standing JF, Tuleu C. Paediatric formulations-getting to the heart of the problem. Int J Pharm 2005; 300: 56-66.
11. Committee on Pediatric AIDS (Section on international child health). Increasing antiretroviral drug access for children with HIV infection, Pediatrics 2007; 119: 838-45.
12. Choonara I, Conroy S. Unlicensed and off-label drug use in children: Implications for safety. Drug Saf 2002; 25: 1-5.
13. Nunn T, Williams J. Formulation of medicines for children. Br J Clin Pharmacol 2005; 59: 674-6.
14. Eileen Kairuz T, Gargiulo D, Bunt C, Garg S. Quality, safety and efficacy in the 'off-label' use of medicines. Curr Drug Safety 2007; 2: 89-95.
15. WHO/Make medicines child size, Available at: http://www.who.int/childmedicines/en/ (accesed 07/2009).
16. Gazzard B (on behalf of the BHIVA Writing Committee). British HIV Association (BHIVA) guidelines for the treatment of HIVinfected adults with antiretroviral therapy (2006). HIV Med 2006; 7: 487-96.
17. Barrueco N, Castillo I, Ais A, et al. Program of pharmaceutic attention to pediatric patients in antiretroviral therapy. Hosp Pharm 2005; 29: 367-74.
18. Brichard B, Van der Linden D. Clinical practice treatment of HIV infection in children. Eur J Pediatr 2009;168: 387-92.
19. Rabel SR, Sun S, Maurin MB. Electronic and resonance effects on the ionization of structural analogues of efavirenz. AAPS PharmSciTech 2001; 3: article 28.
20. Gao JZ, Hussain MA, Motheram R, et al. Investigation of human pharmacoscintigraphic behavior of two tablets and a capsule formulation of a high dose, poorly water soluble/highly permeable drug (Efavirenz). J Pharm Sci 2007; 96: 2970-7.
21. Friedland G, Khoo S, Jack C, Lalloo U. Administration of efavirenz (600 mg/day) with rifampicin results in highly variable levels but excellent clinical outcomes in patients treated for tuberculosis and HIV. J Antimicrob Chemother 2006; 58: 1299-302.
22. Fabbiani M, Di Giambenedetto S, Bracciale L, et al. Pharmacokinetic variability of antiretroviral drugs and correlation with virological outcome: 2 years of experience in routine clinical practice. J Antimicrob Chemother 2009; 64: 109-17.
23. Csajka C, Marzollini C, Fattinger K, et al. Population pharmacokinetics and effects of efavirenz in patients with human immunodeficiency virus infection. Clin Pharm Ther 2003; 73: 20-30.
24. Aarnoutse R, Schapiro JM, Bouchr CAB, et al. Therapeutic drug monitoring. Drugs 2003; 63: 741-53.
25. van Luin M, Gras L, Richter C, et al. Efavirenz dose reduction is safe in patients with high plasma concentrations and may prevent efavirenz discontinuations. J Acquir Immune Defic Syndr 2009; 52: 240-5.
26. Sosnik A, Chiappetta DA, Carcaboso A. Drug delivery systems in HIV pharmacotherapy: What has been done and the challenges standing ahead. J Control Release 2008; 138: 2-15.
27. Wintergerst U, Hoffmann F, Jansson A, et al. Antiviral efficacy, tolerability and pharmacokinetics of efavirenz in an unselected cohort of HIV-infected children, J Antimicrob Chemother 2008; 61: 1336-9.
28. Borrás-Blasco J, Belda A, Rosique-Robles JD, et al. Burning Mouth Syndrome due to efavirenz therapy. Ann Pharmacother 2006; 40: 1471-2.
29. Marcellin F, Boyer S, Protopopescu C, et al. Determinants of unplanned antiretroviral treatment interruptions among people living with HIV in Yaoundé, Cameroon (EVAL survey, ANRS 12-116). Tropical Med Int Health 2008; 13: 1470-8.
30. Starr SE, Fletcher CV, Spector SA, et al. Efavirenz liquid formulation in human immunodeficiency virus-infected children. Pediatr Infect Dis J 2002; 21: 659-63.
31. Bahal SM, Romansky JM, Alvarez FJ. Medium chain triglycerides as vehicle for palatable oral liquids. Pharm Dev Technol 2003; 8: 111-5.
32. Kumar A, Adverse effects of pharmaceutical excipients. Adv Drug React Bull 2003; 222: 851-4.
33. Dutta T, Agashe HB, Garg M, et al. Poly (propyleneimine) dendrimer based nanocontainers for targeting of efavirenz to human monocytes/macrophages in vitro. J Drug Targ 2007; 15: 89-98.
34. Dutta T, Garg M, Jain NK. Targeting of efavirenz loaded tuftsin conjugated poly(propyleneimine) dendrimers to HIV infected macrophages in vitro. Eur J Pharm Sci 2008; 34: 181-9.
35. Sathigar S, Chadha G, Lee Y-HP, et al. Physicochemical characterization of efavirenz-cyclodextrin inclusion complexes. AAPS PharmSciTech 2009; 10: 81-7.
36. Shown I, Murthy CN. Synthesis and characterization of linear water-soluble γ-cyclodextrin based polymers as drug carrier systems. Supramol Chem 2008; 20: 573-8.
37. Alvarez-Lorenzo C, dos Santos FR, Sosnik A, et al. Cyclodextrinbased hydrogels as highly versatile drug delivery systems, In: Hydrogels: Preparation and Applications, Nova Publishers, Columbus F. (Ed.), 2010; in press.
38. th 2005.
39. Chiappetta DA, Carcaboso AM, Rubio MC, et al. Indinavir-loaded pH-sensitive microparticles for taste masking: Toward extemporaneous paediatric anti-HIV/AIDS liquid formulations with improved patient compliance. AAPS PharmSciTech 2009; 10: 1-6.
40. Sosnik A, Amiji M. Nanotechnology solutions for infectious diseases in developing nations. Adv Drug Del Rev 2010; 62: 375-7.
41. Sosnik A, Carcaboso AM, Chiappetta DA. Polymeric Nanocarriers: New endeavors for the optimization of the technological aspects of drugs. Recent Pat Biomed Eng 2008; 1: 43-59.
42. Chiappetta DA, Sosnik A. Poly(ethylene oxide)-poly(propylene oxide) block copolymer micelles as drug delivery agents: Improved hydrosolubility, stability and bioavailability of drugs. Eur J Pharm Biopharm 2007; 66: 303-17.
43. Sosnik A, Chiappetta DA, Hocht C. Aqueous solution pharmaceutical compositions for the oral administration of antiretroviral agents, National Institute of Industrial Property (INPI), Argentina, P090102571, 2009.
44. Chiappetta DA, Hocht C, Taira C, et al. Efavirenz-loaded PEOPPO polymeric micelles: Toward a pediatric anti-HIV pharmacotherapy with significantly higher oral bioavailaibility and reduced inter-individual variability. Nanomedicine 2010; 5: 11-23.
45. Chiappetta DA, Alvarez-Lorenzo C, Rico-Rey A, et al. Nalkylation of poloxamines modulates micellar encapsulation and delivery of the antiretroviral efavirenz. Submitted.
46. Bromberg LE, Ron ES. Temperature-responsive gels and thermogelling polymer matrices for protein and peptide delivery. Adv Drug Del Rev 1998; 31: 197-221.
47. He W, Fan LF, Du Q, et al. Design and in Vitro/in Vivo evaluation of multi-layer film coated pellets for omeprazole. Chem Pharm Bull 2009; 57: 122-8.
48. Han M, Fang Q-L, H-W Zhan, Luo T, Liang W-Q, Gao J-Q. In vitro and in vivo evaluation of a novel capsule for colon-specific drug delivery. J Pharm Sci 2008; 98: 2626-35.
49. Bunupuradah T, Wannachai S, Chuamchaitrakool A, et al. Use of taste-masking product, FLAVORx, to assist Thai children to ingest generic antiretrovirals. AIDS Res Ther 2006; 3: article 30.
50. Sohi H, Sultana Y, Khar RK. Taste masking technologies in oral pharmaceutics: Recent developments and approaches. Drug Dev Ind Pharm 2004; 30: 429-48.
51. Hussein MM, Barcelon SA. Flavor enhancing and medicinal taste masking agent. US Patent #4983394, 1991.
52. Schiffman SS, Gatlin LA, Sattely-Miller EA, et al. The effect of sweeteners on bitter taste in young and elderly subjects. Brain Res Bull 2004; 35: 189-204.
53. de Aquino Ribeiro JA, Moreira de Campos LM, Alves RJ, Portela Lages G, Pianetti GA. Efavirenz related compounds preparation by hydrolysis procedure: Setting reference standards for chromatographic purity analysis. J Pharm Biomed Anal 2007; 43: 298-303.
54. Beckers EJ, Rehrer NJ, Brouns F, et al. Determination of total gastric volume, gastric secretion and residual meal using the double sampling technique of George. Gut 1988; 29: 1725-9.
55. ®) block copolymers. Langmuir 2008; 24: 10688-97.
56. Meadway J. Helping children take HAART adherence, taste and formulations, HIV i-Base - Optimising paediatric HIV care - March 2001; Available at: http://www.i-base.info/pub/paed/help.html (Accessed December 2009).