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Development and Characterization of Microstructured, Spray-Dried Co-Amorphous Mixture of Antidiabetic Agents Stabilized by Silicate

AAPS PharmSciTech volume 20, Article number: 141 (2019) Cite this article

Abstract

In the present work, co-amorphous mixture (COAM) of poorly soluble nateglinide (NT) and highly soluble Metformin hydrochloride (MT) was prepared by spray drying method to improve the dissolution rate of NT and the processability of COAM. Binary spray-dried COAM of NT and MT (120 mg: 500 mg) was prepared in its clinical dose ratio whereas 20% Neusilin®US2 (NS) was added to prepare non-sticky, free flowing ternary COAM. Solubility studies of binary and ternary COAM exhibited sevenfold and tenfold rise in the solubility of NT. Complete amorphization of NT was revealed in XRPD and DSC studies of both COAM and hydrogen-bonding interactions were reflected in FTIR-spectra. SEM microphotographs illustrated round-shaped microparticles in ternary COAM against the irregular particles in binary COAM. In vitro dissolution of NT was significantly improved in ternary COAM > binary COAM > NT irrespective of dissolution medium. On contrary, MT has partially transformed to the amorphous form in COAM without altering the solubility. In accelerated stability studies, NT and MT devitrification was not observed in XRPD of ternary COAM in contrast to binary COAM. Therefore, enhanced dissolution of NT, stabilization of spray-dried dispersion, and its improved processability can be achieved by preparing ternary COAM of NT:MT:NS.

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Acknowledgements

Authors are thankful to Tata Institute of Fundamental Research (TIFR), India for assistance on XRPD and SEM analysis. The authors are highly thankful to Cipla Ltd., India, and Sanofi Ltd., India for providing gift sample of nateglinide and metformin hydrochloride respectively.

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  1. Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKMs NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai, Maharashtra, 400056, India

    Sarika Wairkar & Ram Gaud

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  1. Sarika Wairkar
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  2. Ram Gaud
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Correspondence to Sarika Wairkar.

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Wairkar, S., Gaud, R. Development and Characterization of Microstructured, Spray-Dried Co-Amorphous Mixture of Antidiabetic Agents Stabilized by Silicate. AAPS PharmSciTech 20, 141 (2019). https://doi.org/10.1208/s12249-019-1352-9

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  • DOI: https://doi.org/10.1208/s12249-019-1352-9

KEY WORDS

  • Co-amorphous mixture
  • enhanced dissolution
  • improved processability
  • nateglinide
  • stabilization of amorphous form