Formulation and evaluation of HPMC and pullulan-based rapidly dissolving films containing cilnidipine nanosuspension

Abstract

Cilnidipine is used to treat hypertension. However, it has poor solubility and undergoes extensive first-pass metabolism, which leads to poor bioavailability. This work aimed to prepare rapidly dissolving films (RDFs) containing nanosuspension of CLD with HPMC and pullulan as film-formers. These RDFs deliver the drugs through the buccal mucosa and bypass the first-pass metabolism, thereby increasing bioavailability.

Highlights

Cilnidipine nanosuspension was prepared by the solvent-antisolvent technique in combination with high-speed homogenization.

Rapidly dissolving films were prepared by the solvent casting process using HPMC and pullulan as film formers.

Films containing nanosuspension had a significantly higher release and permeation rate.

Films containing nanosuspension demonstrated better bioavailability and therapeutic efficacy.

The nanosuspension was prepared using the nanoprecipitation technique and was optimized using the CCD. The optimized formulation had an average size and zeta potential of 362.23 nm and −39.1 mV, respectively. FT-IR studies indicated no interaction between CLD and stabilizers. DSC and XRD studies confirmed reduced crystallinity of CLD. SEM revealed the capsular morphology of nanoparticles. The optimized RDFs had a 2.83 ± 0.24 tensile strength, 11.61 ± 2.87 % elongation, 17.21 ± 1.06 s disintegration time, and in-vitro release of 91.77 ± 6.22 % in 60 min.

A more than two-fold increase in drug permeation was recorded from the CLD NS-RDF as compared to the CLD CD-RDF. The CLD NS-RDF exhibited a significant increase in AUC_0-24h, C_max, and a decrease in T_max and MRT as compared to the CLD CD-RDF. The CLD NS-RDF also had a superior effect to control the blood pressure in rats as compared to the CLD CD-RDF.

Materials

CLD was acquired as a gift sample from M/s Windlas Biotech Pvt. Ltd., Dehradun, Uttarakhand, India. Lecithin and sodium lauryl sulphate (SLS) was obtained from Sigma Aldrich, Bengaluru, India. Poloxamer 188 was obtained from BASF India Pvt. Ltd., Bengaluru, India. Pullulan was obtained as a gift sample from Hayashibara, Japan, supplied by Gangwal Chemicals, Mumbai, India. Hydroxypropyl methyl cellulose (HPMC) E5 was procured from Colorcon Limited, Goa, India. Polyvinyl alcohol (PVA).

Shirleen Miriam Marques, Salwa, Cheryl Rhea Lewis, Vasudha Devi, Lalit Kumar, Formulation and evaluation of HPMC and pullulan-based rapidly dissolving films containing cilnidipine nanosuspension, International Journal of Biological Macromolecules, 2025, 143329, ISSN 0141-8130, https://doi.org/10.1016/j.ijbiomac.2025.143329.