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Study on Loratadine Self-microemulsifying Drug Delivery System

Author: LiHaiYan
Tutor: QuanDongQin
School: Central South University
Course: Pharmacy
Keywords: Loratadine self-microemulfying drug delivery system dissolution bioavailability
CLC: R943
Type: Master's thesis
Year: 2013
Downloads: 36
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Abstract

Loratadine (LOR), is a second-generation antihistamine drug and selective histamine H1-receptor antagonist,has been used to relieve the symptoms of allergic rhinitis and other allergies.Now,LOR is marked in dosage forms of tablets,syrups and capsules.LOR is a BCS class Ⅱ drug,with low solubility and high permeability.For this drug,oral absorption is limited by solubility and dissolution. The main objective of this study is to prepare SMEDDS containing LOR to improve its dissolution in vitro and bioavailability in vivo.The HPLC analytic methods for assessment of the LOR content and related substance were established within the pre-formulation study.LOR was liner over the range of1～40μg·ml-1and value of limit of quantitation was200ng·ml-1.This method was proved to be accurate,reliable and reproducible.The partition coefficient value of LOR in octanol/distilled water is2.43.The solubility of LOR decreases with respect to the increase of pH value.Following tests between solubility of LOR in various materials and compatibility of oil phase and surfactant,MCT and EL-35were selected as oil phase and surfactant,respectively.By drawing the ternary phase diagrams with1,2-PRO and PEG400.Five SMEDDS formulations of LOR were prepared and evaluated according to appearance,particle size,Zeta potential, emulsification rate stability and dissolution.The optimized formula was selected to have the smallest particle size (28.15±1.65nm)The dissolution test of the SMEDDS formulation was performed using dissolution apparatus Ⅱ Chinese Pharmacopoeia (2010) in500ml distilled water.The in vitro dissolution of the LOR from SMEDDS was tested by comparison with commercial tablets in among0.1N hydrochloric acid solution, acetate buffer solution, phosphate buffer solution and distilled water.LOR dissolution of SMEDDS is more than80%within30min,However,the release of LOR tablets are less than40% within30min except for in0.1N hydrochloric acid solution.The LOR release from SMEDDS is not affected by pH of the dissolution media comparing with tablets.The LC-MS/MS method has been established for determination of LOR in beagle dogs plasma and to evaluate pharmacokinetic behavior in vivo.The limit of quantification was0.005ng·ml-1and the vaue of method recoveries is between93.41%and100.71%indicating that the LC-MS/MS method was accute.The in vivo test showed an obvious enhancement in LOR oral absorption from SMEDDS compared to commercial tablet.The C max and AUC0-t of SMEDDS were about ninefold and fivefold higher than that of LOR tablet respectively.The three batch of LOR SMEDDS soft capsules were investigated for stability test.The results of stress testing showed LOR SMEDDS should be store in cool and dry place avoiding direct sunshine.Products were stable after accelerated test for3months and long-term test for3months.In conclusion, the dissolution rate in vitro and absorption in vivo of LOR can be increased significantly with SMEDDS formulation. SMEDDS was stable physically and feasible to manufacture. It provids a new dosage form for poor-water soluable drugs.(29figures,40tables,36references)

Study on Loratadine Self-microemulsifying Drug Delivery System

Abstract

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