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Development and pharmacokinetic evaluation of osmotically controlled drug delivery system of Valganciclovir HCl for potential application in the treatment of CMV retinitis

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Abstract

Valganciclovir HCl (VGH) is the widely used drug for the treatment of cytomegalovirus (CMV) retinitis infection with an induction dose of 900 mg per oral (p.o.) twice a day and a maintenance dose of 900 mg (p.o.). This required dose of the drug also leads to multiple side effects due to repeated administration. The research was highlighted to develop, formulate, optimize, and evaluate single-core osmotic pump (SCOP) tablet of VGH with the dose of 450 mg to reduce dosing frequency and associated side effects. The decrease in dose also minimizes the hepatic and nephrotic load. The optimized batch of the formulation was subjected to comparative in vitro and in vivo evaluation. The tablet core composition is the primary influencer of the drug delivery fraction in a zero order, whereas the membrane characteristics control the drug release rate. In vivo pharmacokinetic studies revealed that the newly developed osmotic formulation has controlled zero-order release for 24 h with a single dose of 450 mg while the marketed formulation requires twice administration within 24 h to maintain the plasma concentration in the therapeutic window. The pharmacokinetic study demonstrated that the developed formulation has the area under curve (AUC) of 58.415 µg h/ml with single dose while the marketed formulation shows the AUC of about 37.903 µg h/ml and 31.983 µg h/ml for first and second dose, respectively. The large AUC demonstrates the extended release of drug with a single dose and effective plasma concentration. Hence, the developed formulation can be a promising option for the treatment of CMV retinitis with the minimum dose and dosing frequency.

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The data or analysis during the current study will be made available on request by the corresponding author.

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Acknowledgements

The authors thank Wockhardt Research Centre, Aurangabad and Dr. Reddy’s Hyderabad for providing the gift samples of drugs and excipients. The authors are grateful to the School of Pharmacy, Swami RamanandTeerthMarathwada University, Vishnupuri, Nanded, Maharashtra, India, for providing facilities to carry out the research work.

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Authors and Affiliations

  1. Department of Pharmaceutical Science, School of Pharmacy, Swami Ramanand Teerth Marathwada University, Vishnupuri, 431606, Maharashtra, India

    Ramakanth Gundu, Sanjay Pekamwar & Deepak Kulkarni

  2. Department of Pharmaceutics, Srinath College of Pharmacy, Bajaj Nagar, Waluj, MIDC, Aurangabad, 431136, Maharashtra, India

    Santosh Shelke & Deepak Kulkarni

  3. Department of Pharmacy, Integrated Institute of Technology, Dwarka Sector-9, New Delhi, 110077, India

    Dipak Gadade

  4. Shree Goraksha College of Pharmacy & Research Centre, Khamgaon, 431151, Maharashtra, India

    Santosh Shep

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  1. Ramakanth Gundu
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Contributions

Author RG performed the complete research work. Author SP guided for the proposed research work. The result analysis and interpretation are done by author SS. Author DK and DG contributed to the writing and editing of the manuscript. Author SS contributed for revising the manuscript during major revisions through result analysis, development of new graphics, and by removing grammatical and sentence errors. All the authors approved the manuscript for submission.

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Correspondence to Ramakanth Gundu.

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All animal experiments were approved by the Animal Ethical Committee of Wockhardt Research Center, Aurangabad. All institutional and national guidelines for the care and use of laboratory animals were followed.

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Gundu, R., Pekamwar, S., Shelke, S. et al. Development and pharmacokinetic evaluation of osmotically controlled drug delivery system of Valganciclovir HCl for potential application in the treatment of CMV retinitis. Drug Deliv. and Transl. Res. 12, 2708–2729 (2022). https://doi.org/10.1007/s13346-022-01122-9

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