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Self microemulsifying particles of loratadine for improved oral bioavailability: preparation, characterization and in vivo evaluation

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Abstract

The objective was to study the phase behavior of different formulations, to identify the micro emulsion area and to prepare solid SMEDDS particles (SSMED) of loratadine (LOR) for improving oral bioavailability (BA). Formulations were prepared with either Lauroglycol 90 or Peceol as oils, Solutol HS15 as surfactant and Transcutol P as co-surfactant. Then water titrations were done to know the phase behavior to identify microemulsion zone. The SSMEDs were prepared by physical adsorption on novel silicon based porous particulate carriers. The flow properties of SSMEDs were studied. SSMED with syloid XDP (SSMED-XS) was optimized based on the free flowing nature. The optimized formulation was evaluated for self microemulsifying efficiency, size, PDI, Zeta potential (ZP), robustness in different pH conditions, surface morphology and in vitro release studies. Further, the pharmacokinetic (PK) behavior of SSMEDs was evaluated in wistar rats. The optimized L-SMEDDS formulation possessed a mean globule size of 140.90 ± 2.01 nm. Stearyl amine at 1% level was added as positive charge inducer. The PXRD and SEM studies indicated loss of crystallinity of the drug. In vitro % drug release for LOR powder was 65% and for L and SSMED was ranging in between 95–99% in 2 h. The BA of SSMED with stearyl amine (SSMED-XS) was 2.28 fold (p < 0.05); S-SMEDDS without stearyl amine (SSMED-X) was 1.78 fold (p < 0.001) more, when compared with plain LOR suspension. Cationic SSMEDs showed significant difference over negatively charged SSMED during in vivo studies. The SSMED-XS was found to be stable upto 3 months at room temperature (RT).

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Acknowledgements

One of the authors Mr. Katla Venu Madhav acknowledges AICTE, New Delhi, India for QIP fellowship to carry out this research work. The authors are grateful to M/s Aurobindo Pharma, Hyderabad for providing gift sample of loratadine. The authors are also grateful to M/s Abitec Corporation, USA and M/s Gattefosse, France for the generous gift samples of oils and surfactants. The authors acknowledge the help of M/s Fuji Chemicals, Japan for gift samples of Neusilin US2, Sylysia, M/s Grace & Co for gift samples of Syloid XDP, Syloid 244FP and M/s ACE capsules, Mumbai for gift samples of hard gelatin capsules. The funding was provided by All India Council for Technical Education (Grant No. PHR/724/12). The authors report no conflict of interest. The authors are alone responsible for the content and writing of this paper.

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  1. Department of Nanotechnology, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Telangana, 506009, India

    Katla Venu Madhav

  2. Department of Pharmaceutics, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Telangana, 506009, India

    Veerabrahma Kishan

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  1. Katla Venu Madhav
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Correspondence to Veerabrahma Kishan.

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Madhav, K.V., Kishan, V. Self microemulsifying particles of loratadine for improved oral bioavailability: preparation, characterization and in vivo evaluation. J. Pharm. Investig. 48, 497–508 (2018). https://doi.org/10.1007/s40005-017-0344-6

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