FABRICATION OF AN ABUSE DETERRENT AND MICROEMULSION-BASED SUBLINGUAL FILM OF BUPRENORPHINE HYDROCHLORIDE FOR BREAKTHROUGH PAIN MANAGEMENT
Objective: The present research work aims to develop an abuse deterrent rapidly dissolving buprenorphine microemulsion loaded sublingual film for the treatment of breakthrough pain.
Methods: The Buprenorphine microemulsion loaded sublingual films were prepared using Capmul MCM C8 (oil), tween 20 (surfactant) and propylene glycol (co-surfactant) with different grades of film-forming polymer (HPMC) using film casting machine. The films were evaluated for in vitro disintegration and dissolution study, tensile strength, folding endurance, content uniformity, surface pH, thickness and weight variation, % loading of buprenorphine microemulsion in sublingual film, scanning electron microscope, ex vivo permeation study, droplet size and polydispersity index, Zeta potential, % moisture content, stability and abuse deterrent potential were evaluated.
Results: The optimized film formulation showed desired mechanical properties with minimum disintegration time of 21s and exhibited 34.45 % loading of Buprenorphine microemulsion. Permeation studies through goat sublingual mucosa, indicated 87% Buprenorphine release, through Buprenorphine microemulsion loaded sublingual film, whereas only 30% Buprenorphine release when it was directly added to film without microemulsion strategy.
Conclusion: The present study concludes that abuse deterrent and fast acting buprenorphine microemulsion-incorporated sublingual film of buprenorphine HCL and naloxone HCL is a promising alternative to mostly marketed buprenorphine injectable delivery systems and a non-invasive route of administration for breakthrough pain management.
2. Everhart ET, Cheung P, Shwonek P. Subnanogram-concentration measurement of buprenorphine in human plasma by electron-capture capillary gas chromatography: application to pharmacokinetics of sublingual buprenorphine. Clin Chem 1997;43:2292–302.
3. Dailymed. Available from: https://dailymed.nlm.nih.gov/ dailymed/search.cfm?labeltype=alland query=buprenorphine [Last accessed on 02 Apr 2016].
4. Rxlist. Available from: http://www.rxlist.com/script/ main/srchcont_rxlist.asp?src=buprenorphine andx=0andy=0 [Last accessed on 02 Apr 2016].
5. US-FDA Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. Available from: http://www.accessdata.fda.gov/scripts/cder/ob/docs/tempai.cfm [Last accessed on 02 Apr 2016]
6. Finn A, Vasisht N. Abuse-resistant mucoadhesive devices for delivery of buprenorphine. U. S. Patent 8,703,177; 2014.
7. Bai SA, Xiang QQ. Evaluation of the pharmacokinetics of single and multiple dose buprenorphine buccal film in healthy volunteers. Clin Ther 2016;8:1-12.
8. Elsheikh MA, Elnaggar YS, Gohar EY. Nanoemulsion liquid preconcentrates for raloxifene hydrochloride: optimization and in vivo appraisal. Int J Nanomed 2012;7:3787-802.
9. Myeres GL, Hilbert SD, Boone BJ. Sublingual and buccal film compositions. Patent application US 2011/0,033,541A1; 2009.
10. Guo JH. Bioadhesive polymer buccal patches for buprenorphine controlled delivery: formulation, in vitro adhesion and release properties. Drug Dev Ind Pharm 1994;20:2809-21.
11. Finn A, Vasisht N. Abuse-resistant mucoadhesive devices for delivery of buprenorphine. U. S. Patent 8,703,177; 2014.
12. Daniulaityte R, Falck R, Carlson RG. Illicit use of buprenorphine in a community sample of young adult non-medical users of pharmaceutical opioids. Drug Alcohol Depend 2012;122:201-7.
13. Yokell MA, Zaller ND, Green TC. Buprenorphine and buprenorphine/naloxone diversion, misuse, and illicit use: an international review. Curr Drug Abuse Rev 2011;4:28–41.
14. Uosukainen H, Kauhanen J, Voutilainen S. Twelve-year trend in treatment seeking for buprenorphine abuse in finland. Drug Alcohol Depend 2013;127:207-14.
15. Uosukainen H, Iiomaki J, Kauhanen J. Factors associated with buprenorphine compared to amphetamine abuse among clients seeking treatment in finland. J Subst Abuse Treat 2014;46:561-6.
16. Johanson CE, Arfken CL, Menza SD. Diversion and abuse of buprenorphine: findings from national surveys of treatment patients and physicians. Drug Alcohol Depend 2012;120:190-5.
17. Mundhey DA, Sapkal NP, Daud AS. Optimization, characterization and in vitro evaluation of buprenorphine microemulsion. Int J Pharm Sci Rev Res 2020;60:67-75.
18. Nafee NA, Boraie NA, Ismail FA. Design and characterization of mucoadhesive buccal patches containing cetylpyridinium chloride. Acta Pharm 2003;53:199-212.
19. Gould K, Desai H, Kumar TMP. Preparation and evaluation of novel buccal adhesive system. AAPS PharmSciTech 2004;5:1-9.
20. Irfan M, Rabel S, Bukhtar Q. Orally disintegrating films: a modern expansion in drug delivery system. Saudi Pharm J 2015;24:537-46.
21. Mundhey DA, Rajkondawar VV, Daud AS. A study of method development, validation and forced degradation for quantification of Buprenorphine hydrochloride in a microemulsion formulation. J Appl Pharm Sci 2016;6:159-69.
22. United States Food and Drug Administration (US FDA) Buprenorphine Dissolution Database. Available from: https://www.accessdata.fda.gov›Drug Databases›Dissolution Methods [Last accessed on 26 Dec 2015]
23. Kumar GP, Phani AR, Prasad RG. Polyvinylpyrrolidone oral films of enrofloxacin: film characterization and drug release. Int J Pharm 2014;471:146–52.
24. Kaur G, Singh D, Brar V. Bioadhesive okra polymer based buccal patches as platform for controlled drug delivery. Int J Biol Macromol 2014;70:408–19.
25. Govindasamy P, Kesavan BR, Narasimha JK. Formulation of unidirectional release buccal patches of carbamazepine and study of permeation through porcine buccal mucosa. Asian Pac J Trop Biomed 2013;3:995-1002.
26. United States Food and Drug Administration (US FDA) Abuse-Deterrent Opioids–Evaluation and Labeling, Guidance for Industry. Available from: https://www.fda.gov/downloads/ Drugs/Guidances/UCM334743.pdf. [Last accessed on 26 Dec 2015].
27. Darwish MK, Elmeshad AN. Buccal mucoadhesive tablets of flurbiprofen: characterization and optimization. Drug Discovery Ther 2009;3:181–9.
28. Wiegand TJ, Bettendorf JA, Horowitz BZ. Medscape. Buprenorphine/naloxone toxicity. Available from: emedicine.medscape.com/article/1641147-overview. [Last accessed on 18 Mar 2017].
29. The National Alliance of Advocates for Buprenorphine treatment. Buprenorphine (Suboxone®, Subutex®, Zubsolv®, Bunavail®) is an opioid medication used to treat opioid addiction in the privacy of a physician’s office. Available from: http://www.naabt.org/about_us.cfm. [Last accessed on 18 Mar 2017].
30. Myers LG. Sublingual and buccal film compositions. U. S. Patent 8,475,832; 2013.
31. Nidhin M, Indumathy R, Sreeram KJ. Synthesis of iron oxide nanoparticles of narrow size distribution on polysaccharide templates. Bull Mater Sci 2008;31:93–6.
32. Kumar R, Sinha VR. Preparation and optimization of vornicazole microemulsion for ocular delivery. Colloids Surf B 2014;117:82–8.
33. Quaglia F, Ostacolo L, Mazzaglia A. The intracellular effect of non-ionic amphiphilic cyclodextrin nanoparticles in the delivery of anticancer drugs. Biomaterials 2009;30:374-82.
This work is licensed under a Creative Commons Attribution 4.0 International License.