In Vitro and Biological Evaluation of Oral Fast-Disintegrating Films Containing Ranitidine HCl and Syloid® 244FP-Based Ternary Solid Dispersion of Flurbiprofen

Aisha Rashid; Muhammad Irfan; Yousaf Kamal; Sajid Asghar; Syed Haroon Khalid; Ghulam Hussain; Abdulrahman Alshammari; Thamer H Albekairi; Metab Alharbi; Hafeez Ullah Khan; Zunera Chauhdary; Thierry F Vandamme; Ikram Ullah Khan

doi:10.3390/pharmaceutics16020164

In Vitro and Biological Evaluation of Oral Fast-Disintegrating Films Containing Ranitidine HCl and Syloid^® 244FP-Based Ternary Solid Dispersion of Flurbiprofen

Pharmaceutics. 2024 Jan 24;16(2):164. doi: 10.3390/pharmaceutics16020164.

Affiliations

¹ Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan.
² Hamdard Institute of Pharmaceutical Sciences, Hamdard University Karachi, Islamabad Campus, Islamabad 45550, Pakistan.
³ Department of Physiology, Faculty of Life Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan.
⁴ Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
⁵ Department of Pharmaceutics, College of Pharmacy, University of Sargodha, Sargodha 40100, Pakistan.
⁶ Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad 38000, Pakistan.
⁷ Centre de Recherche en Biomédecine de Strasbourg (CRBS), Inserm/Unistra, UMR 1260 Regenerative NanoMedecine, Université de Strasbourg, 1 Rue Eugène Boeckel, 67000 Strasbourg, France.

Abstract

Flurbiprofen (FBP), a nonsteroidal anti-inflammatory drug (NSAID), is commonly used to treat the pain of rheumatoid arthritis, but in prolonged use it causes gastric irritation and ulcer. To avoid these adverse events of NSAIDs, the simultaneous administration of H₂ receptor antagonists such as ranitidine hydrochloride (RHCl) is obligatory. Here, we developed composite oral fast-disintegrating films (ODFs) containing FBP along with RHCl to provide a gastroprotective effect as well as to enhance the solubility and bioavailability of FBP. The ternary solid dispersion (TSD) of FBP was fabricated with Syloid^® 244FP and poloxamer^® 188 using the solvent evaporation technique. The synthesized FBP-TSD (coded as TSD) was loaded alone (S1) and in combination with plain RHCl (S2) in the composite ODFs based on hydroxypropyl methyl cellulose E5 (HPMC E5). The synthesized composite ODFs were evaluated by in vitro (thickness, folding endurance, tensile strength, disintegration, SEM, FTIR, XRD and release study) and in vivo (analgesic, anti-inflammatory activity, pro-inflammatory cytokines and gastroprotective assay) studies. The in vitro characterization revealed that TSD preserved its integrity and was effectively loaded in S1 and S2 with optimal compatibility. The films were durable and flexible with a disintegration time ≈15 s. The release profile at pH 6.8 showed that the solid dispersion of FBP improved the drug solubility and release when compared with pure FBP. After in vitro studies, it was observed that the analgesic and anti-inflammatory activity of S2 was higher than that of pure FBP and other synthesized formulations (TSD and S1). Similarly, the level of cytokines (TNF-α and IL-6) was also markedly reduced by S2. Furthermore, a gastroprotective assay confirmed that S2 has a higher safety profile in comparison to pure FBP and other synthesized formulations (TSD and S1). Thus, composite ODF (S2) can effectively enhance the FBP solubility and its therapeutic efficacy, along with its gastroprotective effect.

Keywords: HPMC E5; Syloid® 244FP; composite films; flurbiprofen; poloxamer® 188; ranitidine hydrochloride; solid dispersion.

Grants and funding

RSPD2023R568/King Saud University