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Enhancement in Dissolution Rate of Atorvastatin Trihydrate Calcium by Formulating Its Porous Tablet Using Sublimation Technique

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Abstract

Objective

Proposed study was aimed to formulate and evaluate atorvastatin trihydrate calcium porous tablet.

Methods

Since atorvastatin trihydrate calcium is highly unstable drug and is immensely susceptible to hydrolysis and oxidation process, sublimation technique is taken into account for preparing porous tablet by using direct compression technique. Excipient screening and pre-formulation study was conducted to evaluate the presence of drug-excipient compatibility. Formulation was optimised using central composite design (CCD) and optimized batch was further characterised by scanning electron microscopy (SEM) for identification of surface topography. Optimized formulation was also characterised with respect to FTIR, TGA analysis, compression analysis, in vitro drug release studies and stability studies.

Results

Hardness, friability, disintegration time and drug content of optimized porous tablets were found to be 3.46 kg/cm2, 0.92%, 7.23 s and 97.00%, respectively. Compression analysis showed optimized formulation powder is soft and plastic in nature. Tensile strength studies revealed that the tensile strength increases with increase in compression pressure. SEM studies confirmed the presence of number of pores with less than 10 μm pore size. FTIR and TGA studies confirmed that there is no change in chemical structure of drug even in porous tablet. Prepared porous tablets released 85.06 ± 15.55% of drug in 25 min whereas immediate release marketed tablets and pure drug released only 59.13 ± 4.78% and 11.36 ± 2.90% of drug in a same time. The release of proposed dosage form was substantially greater than the marketed product. Preliminary profile of stability studies did not show any significant change (p > 0.05) in the results after 90 days.

Conclusion

Porous tablets improved release rate which confirmed that this approach may be useful to enhance the dissolution rate of atorvastatin trihydrate calcium.

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Acknowledgements

The authors are thankful to Dr. Reddy Laboratories, Hyderabad, for providing atorvastatin trihydrate calcium as a gift sample. Authors gratefully acknowledge the help of Dr. Praveen Khullar, Mr. D. Saravanan and Dr. Prakash Muthudoss, Sanofi-Synthelabo (India) Pvt. Ltd., Verna, Goa, for thermogravimetric analysis of samples. Authors are thankful to Flamingo Pharmaceutical Ltd., Mumbai, for Karl Fisher Titrimetry study. Authors are also thankful to Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education and Goa College of Pharmacy for providing the infrastructural facilities to complete this work.

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Authors and Affiliations

  1. Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, 576 104, India

    Shikha Y. Singh,  Salwa & Lalit Kumar

  2. Department of Pharmaceutics, Goa College of Pharmacy, Panaji, Goa, 403001, India

    Rupesh K. Shirodkar

  3. Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Udupi, Karnataka, 576 104, India

    Ruchi Verma

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  1. Shikha Y. Singh
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Correspondence to Lalit Kumar.

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Singh, S.Y., Salwa, Shirodkar, R.K. et al. Enhancement in Dissolution Rate of Atorvastatin Trihydrate Calcium by Formulating Its Porous Tablet Using Sublimation Technique. J Pharm Innov 15, 498–520 (2020). https://doi.org/10.1007/s12247-019-09397-1

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