Press-Coated Aceclofenac Tablets for Pulsatile Drug Delivery: Formulation and In Vitro Evaluations

Abstract

The symptoms of some diseases show circadian rhythms, such as the morning stiffness associated with pain at the time of awakening in rheumatoid arthritis. Therapy for such diseases doesn't require immediate release or sustained release of medicament. In such therapies, pulsatile drug release is more suitable with a programmed drug release. The purpose of this research was to formulate press-coated aceclofenac tablets for pulsatile drug delivery with a distinct delay time of no drug release and release of the drug when it is more likely desired (i.e., after 5 to 6 h). Immediate release core tablets having aceclofenac were formulated. Three formulations, F1, F2, and F3, were prepared with variable concentrations of sodium croscarmellose. Pre- and post-compression tests were performed on the core tablets. The selection criteria included the lowest disintegration time as a requirement of pulsatile drug delivery with an immediate release core and a delayed release coat. The disintegration times of F1, F2, and F3 were 120 s, 60 s, and 15 s, respectively. Therefore, the F3 formulation was selected as the core tablet formulation because it had the shortest disintegration time (15 s). The core tablets were press-coated using different polymers, such as HPMC K100M, Eudragit L100, HEC, and HPMC E5. The polymers were used in the coatings to hinder the release of the core for the desired time. 36 formulations of polymer were prepared: A1 to A10 had HPMC K100M and Avicel PH102; formulations B1 to B6 had HPMC K100M, Eudragit L100, and Avicel PH102; formulations C1 to C7 had HPMC K100M and hydroxyethyl cellulose; formulations D1 to D7 had HPMC K100M and HPMC E5; and formulations E1 to E6 had changed the coating weight of the formulation used for D6 (having HPMC K100M and HPMC E5 in the ratio of 12.5% to 87.5%). Evaluations of the press-coated tablets were carried out through thickness, hardness, weight variation, friability, and in vitro dissolution tests. These parameters concluded that the formulation of E6, having HPMC K100M and HPMC E5 in the ratio of 12.5% to 87.5% at 600 mg weight, was the most optimum formulation as it showed 3.5% drug release after 4 h, 21.4% drug release after 5 h, and 99.27% drug release after 6 h.

Keywords: FTIR; HEC; HPMC; NSAIDs; pulsatile drug delivery.

Figure 1

FTIR of aceclofenac (A) and press-coated tablet with HPMC E5 (B). The characteristic peaks of the aceclofenac spectrum are 1715, which shows C=O stretching; 1255, which shows C-O stretching; 3318, which shows N-H stretching; 2937, which shows C-H stretching; 748, which shows aromatic—H stretching; and 610, which shows C-Cl stretching.

Figure 2

The in vitro dissolution of formulations A1 to A10 (the first 2 h in an acidic medium of pH 1.2, and then in a phosphate buffer medium of pH 6.8) showing that none of the formulations met the expected criteria for pulsatile drug release.

Figure 3

The in vitro dissolution of formulations B1 to B6 (the first 2 h in an acidic medium of pH 1.2, then in a phosphate buffer medium of pH 6.8) mimicked that of the formulations B1 to B3, which had 100% drug release, though formulations B4 to B6 failed to completely release before 6 h.

Figure 4

The in vitro dissolution of formulations C1 to C7 (the first 2 h in an acid medium of pH 1.2, and then in a phosphate buffer medium of pH 6.8) showing that all formulations failed to release the drug even after 6 h.

Figure 5

The in vitro dissolution of formulation D1 to D7 (the first 2 h in an acid medium of pH 1.2, and then in a phosphate buffer medium of pH 6.8) showing the desired drug release after a delay time of 5 to 6 h.

Figure 6

The in vitro dissolution of formulation E1 to E6 (the first 2 h in an acidic medium of pH 1.2, then in a phosphate buffer medium of pH 6.8) prepared after modifying the formulation of D6. The E6 formulation showed promising drug release, as required.