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Study on the Correlation Between Nimodipine (BCS Class II) Solubility, Dissolution Improvement, and Brain Tissue Concentration Through Cocrystallization

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Abstract

Background

Cocrystallization by solvent evaporation was used to enhance the dissolution, physicochemical properties, and bioavailability of nimodipine (NMD). Here, we aimed to develop NMD cocrystals with improved solubility and dissolution. Thereafter, our objective was to check the changes in brain tissue concentrations before and after the cocrystal formation of NMD.

Methods

A 32-factor design was used for product optimization by determining the desirability function. Differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy were used to confirm the formation of cocrystals.

Results

The saturation solubility study of NMD:SA cocrystals resulted in 9.52 mg/ml, which is 128-fold higher than that of pure NMD (0.074 mg/ml). In vitro dissolution and permeability studies showed an improvement in the percentage of drug release and permeability of NMD from cocrystals as compared to pristine NMD. An in vivo study of oral bioavailability in Wistar rats demonstrated higher plasma and brain tissue concentrations of NMD in the cocrystal form than in the conventional oral suspension.

Discussions

The findings of this study showed a positive correlation between nimodipine solubility, improvement in dissolution, and its effect on brain tissue concentration in Wistar rats. The improved solubility of nimodipine may lead to increased dissolution rates, which can enhance its bioavailability and therapeutic efficacy in the treatment of cerebral vasospasms.

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Data Availability

Data will be made available on request to authors.

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Funding

This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. B K Mody Government Pharmacy College, Government Polytechnic Campus, Nr Aji Dam, Rajkot, 360003, Gujarat, India

    Nilam Rathod, Chetan Borkhataria, Ravi Manek, Vidhi Patel, Nilesh Patel, Kalpesh Patel & Jalpa Paun

  2. Gujarat Technological University, Ahmedabad, Gujarat, India

    Dhruv Sakhiya

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  1. Nilam Rathod
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  2. Chetan Borkhataria
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  4. Vidhi Patel
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  7. Jalpa Paun
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Contributions

Nilam Rathod and Vidhi Patel—research; Ravi Manek and Chetan Borkhataria—guidance and article draft. Nilesh Patel, Kalpesh Patel, and Jalpa Paun—calculations and factorial design. Dhruv Sakhiya—inferences and discussion of the results.

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Correspondence to Chetan Borkhataria.

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Rathod, N., Borkhataria, C., Manek, R. et al. Study on the Correlation Between Nimodipine (BCS Class II) Solubility, Dissolution Improvement, and Brain Tissue Concentration Through Cocrystallization. J Pharm Innov 18, 2235–2248 (2023). https://doi.org/10.1007/s12247-023-09786-7

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