(M1030-08-48) Effect of Semi-Synthetic Bases and Hydrophile-Lipophile Balance of Mixed Surfactants on Ibuprofen Suppository Release Profiles

Purpose: Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), is associated with gastrointestinal side effects when administered orally, necessitating alternative delivery routes such as rectal suppositories. The release profile of ibuprofen from suppositories is influenced by the suppository base and additives like surfactants. This study aimed to investigate the impact of semi-synthetic fatty bases, the hydrophilic-lipophile balance (HLB) of mixed surfactants (Tween® 80 and Span® 80), and their concentrations on the in-vitro release kinetics and physical properties of ibuprofen suppositories, with the goal of optimizing rectal drug delivery to enhance bioavailability and patient compliance.

Methods: Ibuprofen suppositories (200 mg) were formulated using the fusion method in 1 g molds with semi-synthetic bases: Witepsol® H15, Witepsol® W35, Witepsol® E85, and Suppocire® CM. Mixed surfactants were incorporated at 4% w/w with HLB values ranging from 4.3 to 15.0, achieved by varying Tween® 80 and Span® 80 ratios. Additional formulations at optimal HLB were prepared with surfactant concentrations of 2% and 6% w/w. Physical properties, including weight uniformity, softening and melting points, crushing strength, and disintegration time, were evaluated per British Pharmacopoeia (2013) standards. In-vitro release studies were conducted using the BP basket method in phosphate buffer (pH 7.4) at 37 ± 1°C, with drug release quantified via UV spectroscopy at 222 nm. Release data were analyzed using zero-order, first-order, Higuchi, and Korsmeyer-Peppas kinetic models to determine release mechanisms. Statistical significance was assessed using ANOVA and t-tests (p = 0.05).

Results: All suppositories met BP weight uniformity standards (95–105% of mean weight). Without surfactants, release followed the order Witepsol® W35 (highest) > Witepsol® H15 > Suppocire® CM > Witepsol® E85 (lowest, < 30% after 180 min), attributed to differences in monoglyceride content and melting points (Witepsol® E85: 40–46°C; others: 37–40°C). Surfactant addition at 4% w/w significantly enhanced release, with optimal HLB values of 4.3–6.0 for Suppocire® CM (up to 53% release) and Witepsol® E85, and 10.0–12.0 for Witepsol® H15 (27.58% at HLB 12, 5 min) and Witepsol® W35 (22.50% at HLB 12, 5 min). Increasing surfactant concentration to 6% w/w at optimal HLB doubled the release rate constant for Suppocire® CM (Higuchi model, R² > 0.95), while 2% w/w showed minimal improvement. Release kinetics predominantly followed the Higuchi model, with non-Fickian (anomalous) transport (n > 0.5) for most formulations, except Suppocire® CM at HLB 12.0 (Fickian, n = 0.11). Surfactants increased crushing strength (e.g., 51.7 ± 7.6 N for Witepsol® E85 at HLB 12) and reduced disintegration times (e.g., 0.7 ± 0.05 min for Witepsol® W35 at HLB 4.3).

Conclusion: The study demonstrates that the type of semi-synthetic base, HLB of mixed surfactants, and surfactant concentration significantly influence ibuprofen release from suppositories. Witepsol® W35 and H15, with higher monoglyceride content, favored release at hydrophilic HLB (10.0–12.0), while Suppocire® CM and Witepsol® E85 performed better at lipophilic HLB (4.3–6.0). Higher surfactant concentrations (6% w/w) enhanced release rates, particularly for lipophilic bases, by improving wetting and solubilization. These findings provide a framework for optimizing ibuprofen suppository formulations to improve bioavailability, offering a promising strategy to mitigate gastrointestinal side effects and enhance patient compliance in NSAID therapy.

Tables showing the code and the physical parameters of the ibuprofen suppositories

Figures showing the release profile of the ibuprofen suppositories in the different bases

Tables showing the release kinetics and the release profile of the ibuprofen suppositories in the different bases