All4Nutra
Abstract
Purpose: To develop aceclofenac hydrogel-based solid dispersions (AC-HSDs) encapsulated in two modified gelatin capsules (MGCs as MGX1 and MGX2) for sustained drug delivery.
Methods: The AC-HSDs were prepared with Eudragit L 100 (EL1 – EL5) and hydroxypropyl methylcellulose acetate succinate (HP1 – HP5) at various drug: carrier ratios (1:1, 1:2, 2:1, 1:3, using solvent evaporation technique and characterized by percentage encapsulation efficiency (EE%), scanning electron microscopy (SEM), differential scanning calorimetry (DSC). In vitro drug release of 10 mg (AC-HSDs) was investigated using USP Type I and in vivo anti-inflammatory study of (AC-HSDs; test), pure aceclofenac, and aceclofenac tablet (positive control; administered orally at 10 mg/kg body) was evaluated using the rat paw edema method.
Result: Eudragit–based solid dispersions showed significantly higher entrapment efficiency compared to hydroxypropyl methylcellulose acetate succinate–based formulation (p < 0.05). The DSC and SEM of both batches revealed discrete particle sizes and shapes with decreased crystallinity. The AC-HSDs encapsulated in MGX1 showed significantly prolonged drug release compared to MGX2 (p < 0.05). Furthermore, HP-SDs showed significantly higher edema inhibition (86 %) compared to pure aceclofenac and commercial aceclofenac tablets (p < 0.05)
Conclusion: Aceclofenac hydrogel-based solid dispersions (AC-HSDs) encapsulated in MGCs show sustained release effects as an alternative technology to deliver aceclofenac.
Introduction
Sustained release drug delivery (SRDD) provides prolonged release of drugs over a long period, thereby achieving good patient-friendly administration with enhanced bioavailability. The basic concept behind SRDD is to improve patient compliance by increasing the bioavailability and effectiveness of the drug substance [1]. This drug delivery is an efficient approach to delivering drugs with short half-lives, particularly when there is need for repetitive dosing. Some merits of SRDD include localized drug effect which reduces dosing frequency, ensuring uniform drug distribution, reducing side effects, stable drug absorption levels in blood and plasma, and patient compliance [2].
Recent studies have focused on the design of SRDD systems for lipophilic drugs [3]. However, when designing such a drug delivery system, some factors must be considered which include half-life and pharmacological effect of the drug. Considering the shortfalls of conventional drug dosing systems (repeated dosing), SRDD achieves uniform drug release over prolonged period, reduced side effects, and favourable therapeutic drug blood levels. Conventional drug delivery methods may be easier and more preferred to deliver some drugs. However, frequent dosing may have several challenges such as poor adherence, low bioavailability, instability, toxicity, and others. Thus, an SRDD aims to maintain drug plasma levels and achieve a steady state.
There are previous works on sustained-release drug delivery (SRDD) using different methods. A sustained solid dispersion of metformin has been prepared to enhance poor permeability across biological membranes and half-life [4]. Hyaluronic acid (HA) sustained release was prepared for wound healing by mixing methacrylate and dopamine to produce a complex which was bonded with arginine derived substance to form hydrogels [5]. Poly (lactic-co-glycolic acid) microsphere was prepared with Doxorubicin-hyaluronate (DOX-HA) micelles to exhibit good sustained release characteristics compared to DOX alone [6]. Also, sustained release was obtained by complexing plasmid DNA with quaternary ammonium chain via electrostatic interaction and slow hydrolysis of ester bond that exposed negatively charged carboxyl groups [7].
Aceclofenac (AC) is a phenylacetic acid derivative group of nonsteroidal anti-inflammatory drugs. It is a class II agent in biopharmaceutical classification systems with poor solubility challenges. It has a poor water solubility of about 60 𝜇g/mL [8]. The substance has a biological half-life of < 4 h, which necessitates numerous daily doses. To maintain its therapeutic effect, the recommended dose ranges from 100 to 200 mg [9]. This is associated with gastrointestinal tract (GIT) disorders when administered orally [10].
The physicochemical challenges associated with aceclofenac (AC) have led to research aimed at finding solutions. Solid dispersions of aceclofenac with subsequent encapsulation in modified gelatin capsules (MGCs) were investigated to enhance its poor aqueous nature, short residence time, and improve its low bioavailability. Therefore, this study investigated aceclofenac hydrogel-based solid dispersions (AC-HSDs) using solvent evaporation technique and encapsulated in two 3-h modified gelatin capsules (MGX1 and MGX2) for prolonged and sustained drug delivery.
Download the full article as PDF here Encapsulation of aceclofenac hydrogel-based solid dispersion for sustained deliveryel-based solid dispersion for sustained delivery
Materials
Aceclofenac (Jagmag Pharm, India), Eudragit® L 100 powder (Evonik, Darmstadt, Germany), Hydroxypropyl methylcellulose acetate succinate (Shin-Etsu, Chem company, Japan), Cremophor® RH 40 (BASF Ludwigshafen, Germany), dialysis membrane (6000 – 8000 Da). All other chemicals are of analytical grade and used as supplied.
Calister E Ugwu*, Kingsley C Eze, Encapsulation of aceclofenac hydrogel-based solid dispersion for sustained delivery, Tropical Journal of Pharmaceutical Research June 2025; 24 (6): 753-760, ISSN: 1596-5996 (print); 1596-9827 (electronic)
Read also our introduction article on Gelatin here:
