DESIGN AND DEVELOPMENT OF SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEMS (SMEDDS) OF TELMISARTAN FOR ENHANCEMENT OF IN VITRO DISSOLUTION AND ORAL BIOAVAILABILITY IN RABBIT
DOI:
https://doi.org/10.22159/ijap.2018v10i4.27048Keywords:
Telmisartan, SMEDDS, Cinnamon essential oil, Gelucire 4414, Transcutol HP, aqueous solubility, dissolution rate, bioavailabilityAbstract
Objective: The main purpose of this investigation was to prepare self-microemulsifying drug delivery system (SMEDDS) for enhancement of oral bioavailability of a poorly water soluble drug telmisartan (TLS), a BCS class II drug by improving its dissolution rate.
Methods: Self-Emulsifying Drug Delivery Systems (SEDDS) of TLS were formulated using cinnamon essential oil as the oil phase, Gelucire 44/14 as the surfactant and Transcutol HP as co-surfactant. Drug-excipient interactions were studied by FTIR spectroscopy. The formulations were evaluated for its self-emulsifying ability, clarity, and stability of the aqueous dispersion after 48 h and the phase diagram was constructed to optimize the system. Selected formulations were characterized in terms of droplet size distribution, zeta potential, cloud point and were subjected to in vitro drug release studies. The bioavailability of optimized formulation was assessed in New Zealand white rabbits.
Results: By considering smaller droplet size, higher zeta potential and faster rate of drug release the formulation TF9 was chosen as optimized SMEDDS formulations. TF9 was robust to different pH media and dilution volumes, remained stable after three cooling-heating cycles and after stored at 4 °C and 25 °C for 3 mo without showing a significant change in droplet size. The pharmacokinetic study in rabbits showed SMEDDS have significantly increased the Cmax and area under the curve (AUC) of TLS compared to suspension (P<0.05).
Conclusion: SMEDDS can be an effective oral dosage form for enhancing aqueous solubility and improving oral bioavailability of poorly water soluble drugs.
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Wang L, Dong J, Chen J, Eastoe J, Li Xuefeng. Design and optimization of a new self-nanoemulsifying drug delivery system. J Colloid Interface Sci 2009;330:443–8.
Hoffman A, Dahan A. Rationalizing the selection of oral lipid based drug delivery systems by an in vitro dynamic lipolysis model for improved oral bioavailability of poorly water soluble drugs. J Controlled Release 2008;129:1–10.
Nagarsenker MS, Date A. Design and evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for cefpodoxime proxetil. Int J Pharm 2007;329:166–72.
Desai PP, Date AA, Patravale VB. Overcoming poor oral bioavailability using nanoparticle formulations–opportunities and limitations. Drug Discovery Today Tech 2012;9:e87-95.
Takagi T, Ramachandran C, Bermejo M, Yamashita S, Yu LX, Amidon GL. A provisional biopharmaceutical classification of the top 200 oral drug products in the United States, Great Britain, Spain, and Japan. Mol Pharm 2006;3:631–43.
Kawabata Y, Wada K, Nakatani M, Yamada S, Onoue S. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: basic approaches and practical applications. Int J Pharm 2011;420:1–10.
Williams HD, Trevaskis NL, Charman SA, Shanker RM, Charman WN, Pouton CW. et al. Strategies to address low drug solubility in discovery and development. Pharmacol Rev 2013;65:315–499.
Palmer AM. New horizons in drug metabolism, pharmacokinetics and drug discovery. Drug News Perspectives 2003;16:57–62.
Weuts I, Kempen D, Decorte A, Verreck G, Peeters J, Brewster M, et al. Phase behaviour analysis of solid dispersions of loperamide and two structurally related compounds with the polymers PVP-K30 and PVP-VA64. Eur J Pharm Sci 2004;22:375–85.
Ammar HO, Salama HA, Ghorab M, Mahmoud AA. Implication of inclusion complexation of glimepiride in cyclodextrin-polymer systems on its dissolution, stability and therapeutic efficacy. Int J Pharm 2006;20:53–7.
Aungst BJ. Novel formulation strategies for improving oral bioavailability of drugs with poor membrane permeation or presystemic metabolism. J Pharm Sci 1993;82:979–87.
Hiendrawan S, Hartanti AW, Veriansyah B, Widjojokusumo E, Tjandrawinata RR. Solubility enhancement of ketoconazole via salt and cocrystal formation. Int J Pharm Pharm Sci 2015;7:160-4.
Odeberg JM, Kaufmann P, Kroon KG, Hoglund P. Lipid drug delivery and rational formulation design for lipophilic drugs with low oral bioavailability, applied to cyclosporine. Eur J Pharm Sci 2003;20:375–82.
Humberstone AJ, Charman WN. Lipid-based vehicles for the oral delivery of poorly water soluble drugs. Adv Drug Delivery Rev 1997;25:103–28.
Constantinides PP. Lipid microemulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects. Pharm Res 1985;12:161–72.
Sisinthy SP, Sarah CYL, Rao NK. Optimization of coconut oil based selfmicro emulsifying drug delivery systems of olmesartan medoxomil by simplex centroid design. Int J Appl Pharm 2016;8:47-52.
Bajaj A, Rao MRP, Pardeshi A, Sali D. Nanocrystallization by evaporative antisolvent technique for solubility and bioavailability enhancement of telmisartan. AAPS Pharm Sci Tech 2012;13:1331–40.
Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Delivery Rev 2000;64:175–93.
Balakrishnan P, Lee BJ, Oh DH, Kim JO, Lee YI, Kim DD, et al. Enhanced oral bioavailability of Coenzyme Q10 by self-emulsifying drug delivery systems. Int J Pharm 2009;374:66-72.
Nazzal S, Smalyukh II, Lavrentovich OD, Khan MA. Preparation and in vitro characterization of a eutectic based semisolid self-nanoemulsified drug delivery system (SNEDDS) of ubiquinone: mechanism and progress of emulsion formation. Int J Pharm 2002;235:247–65.
Villar AM, Naveros BC, Campmany AC, Trenchs MA, Rocabert CB, Bellowa LH. Design and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) for enhanced dissolution of gemfibrozil. Int J Pharm 2012;431:161–75.
Khoo SM, Humberstone AJ, Porter CJH, Edwards GA, Charman WN. Formulation design and bioavailability assessment of lipidic self-emulsifying formulations of halofantrine. Int J Pharm 1998;167:155–64.
Elnaggar YSR, El-Massik MA, Abdallah OY. Self-nanoemulsifying drug delivery systems of tamoxifen citrate: design and optimization. Int J Pharm 200;380:133–41.
Shafiq S, Shakeel F, Talegaonkar S, Ahmad FJ, Khar RK, Ali M. Development and bioavailability assessment of ramipril nanoemulsion formulation. Eur J Pharm Biopharm 2007; 66:227–43.
Zhang P, Liu Y, Feng N, Xu J. Preparation and evaluation of self-microemulsifying drug delivery system of oridonin. Int J Pharm 2008;355:269–76.
Kang BK, Lee JS, Chon SK, Jeong SY, Yuk SH, Khang G, et al. Development of self-microemulsifying drug delivery systems (SMEDDS) for oral bioavailability enhancement of simvastatin in beagle dogs. Int J Pharm 2004;274:65–73.
Anton N, Benoit JP, Saulnier P. Design and production of nanoparticles formulated from nano-emulsion templates-a review. J Controlled Release 2008;128:185–99.
Mc Conville C, Friend D. Development and characterisation of a self-microemulsifying drug delivery systems (SMEDDSs) for the vaginal administration of the antiretroviral UC-781. Eur J Pharm Biopharm 2013;83:322–9.
Davies JT. Drop sizes of emulsions related to turbulent energy-dissipation rates. Chem Eng Sci 1985;40:839–42.
Becher P. Hydrophile-lipophile balance (HLB)-history and recent developments. J Dispersion Sci Tech 1984;5:81–96.
Pouton CW. Lipid formulations for oral administration of drugs: nonemulsifying, self emulsifying and self microemulsifying drug delivery systems. Eur J Pharm Sci 2000;11:S93–8.
Patel AR, Vavia PR. Preparation and in vivo evaluation of SMEDDS (self microemulsifying drug delivery system) containing fenofibrate. AAPS J 2007;9:E344–52.
Pouton CW, Porter CJ. Formulation of lipid-based delivery systems for oral administration: materials, methods and strategies. Adv Drug Delivery Rev 2008;60:625–37.
Anton N, Gayet P, Benoit JP, Saulnier P. Nano-emulsions and nanocapsules by the PIT method: an investigation on the role of the temperature cycling on the emulsion phase inversion. Int J Pharm 2007;344:44–52.
Craig DQM, Barker SA, Banning D, Booth SW. An investigation into the mechanisms of self-emulsification using particle size analysis and low frequency dielectric spectroscopy. Int J Pharm 1995;114:103–10.
Pouton CW. Formulation of self-emulsifying drug delivery systems. Adv Drug Delivery Rev 1997;25:47-58.
Patil P, Patil V, Paradkar A. Formulation of a self-emulsifying system for oral delivery of simvastatin: in vitro and in vivo evaluation. Acta Pharm 2007;57:111-22.
Lindenberg M, Kopp S, Dressman JB. Classification of orally administered drugs on the World Health Organization model list of essential medicines according to the biopharmaceutics classification system. Eur J Pharm Biopharm 2004;58:265-78.
Bandyopadhyay S, Katare OP, Singh B. Optimized self nano-emulsifying systems of ezetimibe with enhanced bioavailability potential using long chain and medium chain triglycerides. Colloids Surf B 2012;100:50-61.
Giongo AL, Vaucher RDA, Ourique AF, Steffler MCR, Frizzo CP, Hennemman B. Development of nanoemulsion containing Pelargonium graveolens oil: characterization and stability study. Int J Pharm Pharm Sci 2016;8:271-6.
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