Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-29T08:56:00.519Z Has data issue: false hasContentIssue false
  • English
  • Français

Formulation and characterization of a paediatric nanoemulsion dosage form with modified oral drug delivery system for improved dissolution rate of nevirapine

Published online by Cambridge University Press:  02 April 2018

Tapiwa E. Manyarara ,
Star Khoza ,
Admire Dube  and
Chiedza C. Maponga
Tapiwa E. Manyarara*
Affiliation:
School of Pharmacy, College of Health Sciences, PO BOX MP 167, University of Zimbabwe.
Star Khoza
Affiliation:
Department of Clinical Pharmacology, College of Health Sciences, University of Zimbabwe, P.O. Box A178, Avondale, Harare, Zimbabwe.
Admire Dube
Affiliation:
School of Pharmacy, University of Western Cape, Robert Sobukwe Road, Bellville, 7535, South Africa.
Chiedza C. Maponga
Affiliation:
School of Pharmacy, College of Health Sciences, PO BOX MP 167, University of Zimbabwe.
*
*Corresponding author: Mr T. Manyarara: School of Pharmacy, College of Health Sciences, PO BOX MP 167, University of Zimbabwe, Email address: tapiwa_ed@hotmail.com
Get access

Abstract

Background: The development of appropriate dosage forms for paediatric antiretroviral therapy is key for improved therapeutic outcomes in children. The focus of this study was to improve solubility, dissolution rate, drug release and maintain high drug permeability.

Methodology: A nanoemulsion was prepared using emulsion inversion point and evaluated. The nanoemulsion had nevirapine (3% w/w). In vitro drug release studies were performed using dialysis membrane. Permeability studies using the Caco-2 cell model were performed for the formulation.

Results: The optimized nevirapine nanoemulsion had a mean droplet size of 36.09±12.27nm, low pdI of 0.598 and zeta potential of -7.87±4.35mV. At pH 2, the nanoemulsion released 76 ± 2 % of nevirapine within 2 h, while at pH 6.4 value representing the small intestine, amount of nevirapine released was 41.6± 4 %. The permeability rate of the nevirapine nanoemulsion was 30.02 x 10-6cm/s and higher than that of propranolol. Efflux ratio was 0.02 indicating low chance of drug efflux occurring.

Conclusion: The results showed that a modified liquid drug release formulations of nevirapine could improve rate of dissolution and maintain high permeability and low drug efflux improving bioavailability of nevirapine in vivo.

Keywords

nanoscalephase transformationbiomedical
Type
Articles
Information
MRS Advances , Volume 3 , Issue 37: African Materials Research Society 2017 , 2018 , pp. 2203 - 2219
Copyright
Copyright © Materials Research Society 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Savjani, KT, Gajjar, AK, Savjani, JK. Drug Solubility: Importance and Enhancement Techniques. ISRN Pharm. 2012 Jul 5;2012.Google Scholar
Shegokar, R, Singh, KK. Nevirapine nanosuspensions for HIV reservoir targeting. Pharmazie. 2010 Nov 16;66:408–15.Google Scholar
Holm, R. FORMULATION STRATEGIES FOR LOW SOLUBLE DRUGS- AN OVERVIEW [Internet]. http://rbbbd.com/pdf/presentations/Ren%E9%20Holm/Amman_sep_2013_reneholm.pdf Date Accessed: 14/05/2015Google Scholar
Nanjwade, BK, Patel, DJ, Udhani, RA. Functions of Lipids for Enhancement of Oral Bioavailability of Poorly Water-Soluble Drugs. Sci Pharm. 2011;79:705–27.CrossRefGoogle ScholarPubMed
Yadollahi, R, Vasilev, K, Simovic, S. Nanosuspension Technologies for Delivery of Poorly Soluble Drugs. 2014 Oct 15;2015 (2015):13.Google Scholar
Riska, P, Lamson, M, MacGregor, T, Sabo, J. Disposition and biotransformation of the antiretroviral drug nevirapine in humans. Drug Metab Dispos. 1999;27(8):895–901.Google ScholarPubMed
1. “Viramune Medication Guide.” [Internet]. Boehringer Ingelheim Pharmaceuticals, Inc.; [cited 2015 Jun 25]. Available from: http://bidocs.boehringer-ingelheim.com/BIWebAccess/ViewServlet.ser?docBase=renetnt&folderPath=/Prescribing+Information/PIs/Viramune/Viramune.pdf. Date Accessed: 25/06/2015Google Scholar
Gupta, MM, Brijesh, R. A Review On: Sustained Release Technology. Int J Ther Appl. 2012;8:18–23.Google Scholar
Mandhar, P, Joshi, G. Development of Sustained Release Drug Delivery System: A Review. ASIAN Pac J Health Sci. 2015;2(1):179–85.Google Scholar
Garg, C, Saluja, V. Once-daily sustained-release matrix tablets of metformin HCL based on an enteric polymer and chitosan. J Pharma Edu Res. 2013;4(1):92–7.Google Scholar
Usach, I, Melis, V, Peris, J-E. Non-nucleoside reverse transcriptase inhibitors: a review on pharmacokinetics, pharmacodynamics, safety and tolerability. J Int AIDS Soc [Internet]. 2013 Sep 4;(16). Available from: http://www.jiasociety.org/index.php/jias/article/view/18567 Date Accessed: 18/04/2015Google Scholar
Kearns, G, Townend, J, Hosseinipour, MC, L’homme, RL, Oko, F. Developmental Pharmacology – Drug Disposition, Action and Therapy in Infants and Children. NEngJMed. 2003;349(12):1157–67.CrossRefGoogle ScholarPubMed
Manyarara, T, Khoza, S, Maponga, C. Pharmacokinetics of Nevirapine in HIV Infected Children from Resource Limited Settings Using Fixed Dose Anti-retroviral Combinations. Br J Pharm Res. 2016 Jul 12;12(3):1–8.CrossRefGoogle Scholar
Neely, M, Rakhmanina, N. Pharmacokinetic optimization of antiretroviral therapy in children and adolescents. Clin Pharmacokinet. 2011 Mar;50(3):143–89.CrossRefGoogle ScholarPubMed
Vanprapar, N, Cressey, TR, Chokephaibulkit, K, Muresan, P, Nottasorn, P. A Chewable Pediatric Fixed-dose Combination Tablet of Stavudine, Lamivudine, and Nevirapine: Pharmacokinetics and Safety Compared With the Individual Liquid Formulations in Human Immunodeficiency Virus-infected Children in Thailand. Pediatr Infect J. 2010 Oct;29(10):940–4.CrossRefGoogle ScholarPubMed
Rakhmanina, N, Phelps, R. Pharmacotherapy of Pediatric HIV Infection. Pediatr Clin North Am. 2013 Oct 1;59(5):1093–115.CrossRefGoogle Scholar
Abrams, Elaine. Developing child-appropriate formulations: what is in the research pipeline for paediatric ARVS? Challenges in the Development &Procurement of Pediatric ARV Formulations. ICAP Columbia University Mailman School of Public Health; 2011.Google Scholar
Guidelines for Antiretroviral Therapy for the Prevention and Treatment of HIV in Zimbabwe. National Medicine and Therapeutics Policy Advisory Committee (NMTPAC) and The AIDS and TB Directorate, Ministry of Health and Child Care; 2013. 88 p.Google Scholar
Jaiswal, M, Dudhe, R, Sharma, PK. Nanoemulsion: an advanced mode of drug delivery system. Biotech. 2015;5:123–7.Google ScholarPubMed
Gupta, H, Eral, B, Hatton, TA, Doyle, P. Nanoemulsions: Formation, Properties and Applications. Soft Matter. 2016;12:2826–41.Google Scholar
Mason, T, Wilking, J, Meleson, K, Chang, C. Nanoemulsions: formation, structure, and physical properties. J Phys Condens Matter. 2006 Sep 29;18:635–66.CrossRefGoogle Scholar
Rakhmanina, N, van den Anker, J. Pharmacological research in pediatrics: From neonates to adolescents. Adv Drug Deliv Rev. 2006 Mar 13;58(1):4–14.CrossRefGoogle ScholarPubMed
Fernandeza, P, Andr´eb, V, Riegera, J. Nano-emulsion formation by emulsion phase inversion, Colloids and Surfaces. Physicochem Eng Asp. 2004 Sep 8;251:53–8.CrossRefGoogle Scholar
Nobbmann, U. FAQ: Peak size or z-average size – which one to pick in DLS? [Internet]. Malvern Instruments; 2014 [cited 2017 Feb 15]. Available from: http://www.materials-talks.com/blog/2014/07/10/faq-peak-size-or-z-average-size-which-one-to-pick-in-dls/ Date Accessed: 15/02/2017Google Scholar
Nidhi, D. In Situ Gel. A novel approach of gastro retentive drug delivery. Asian J Pharm Sci Res. 2013;3(3):1–14.Google Scholar
Kushal, P, Piyush, A, Ashok, D. Formulation and evaluation of oral floatable in-situ gel of ranitidine hydrochloride. J Drug Deliv Ther. 2013;3(3):90–7.Google Scholar
Bhalerao, KK, Pravin, PA, Dange, SM, Rohini, P. A short Review on Stomach Specific Floating in-situ gel. J Biomed Pharm Res. 2012;1(3):1–4.Google Scholar
D’Souza, S. A Review of In Vitro Drug Release Test Methods for Nano-Sized Dosage Forms. Adv Pharm. 2014 Nov 20;2014:12.Google Scholar
In vitro drug absorption [Internet]. Cerep; 2013 [cited 2017 Apr 10]. Available from: http://www.cerep.fr/cerep/users/pages/downloads/Documents/Marketing/Pharmacology%20&%20ADME/Application%20notes/2013/In%20vitro%20drug%20absorption.pdf Date Accessed: 10/04/2017Google Scholar
Volpe, DA. Application of Method Suitability for Drug Permeability Classification. AAPS J. 2010 Dec;12(4):670–8.CrossRefGoogle ScholarPubMed
O’Hagan, S, Kell, DB. The apparent permeabilities of Caco-2 cells to marketed drugs: magnitude, and independence fromboth biophysical properties and endogenite similarities. PeerJ. 3:1–17.Google Scholar
Yuksel, N, Kanik, AE, Baykara, T. Comparison of in vitro dissolution profiles by ANOVA-based, model-dependent and -independent methods. Int J Pharm. 2000 Aug 15;209:57–67.CrossRefGoogle ScholarPubMed
Ketan, P, Sarma, V, Vavia, P. Design and evaluation of Lumefantrine – Oleic acid self nanoemulsifying ionic complex for enhanced dissolution. DARU J Pharm Sci. 2013;21:27–30.Google Scholar
Selvam, RP, Kulkarni, PK. Design and Evaluation of Self Nanoemulsifying Systems for Poorly Water Soluble HIV Drug. J PharmaSciTech. 2014;4(1).Google Scholar
Syed, KH, Al-Assaf, S, Phillips, O Hydrogels, G.: Methods of Preparation, Characterisation and Applications. Progress in Molecular and Environmental Bioengineering – From Analysis and Modeling to Technology Applications [Internet]. [cited 2017 Mar 16]. Available from: http://www.scientificspectator.com/documents/personal%20care%20spectator/Hydrogels.pdf Date Accessed: 16/03/2017Google Scholar
Tadros, TF. Emulsion Formation, Stability, and Rheology. Emulsion Formation and Stability. first. Wiley-VCH Verlag GmbH & Co. KGaA; 2013.CrossRefGoogle Scholar
Honary, S, Zahir, F. Effect of Zeta Potential on the Properties of Nano-Drug Delivery Systems - A Review (Part 2). Trop J Pharm Res. 2013 Apr;12(2):265–73.Google Scholar