The objectives of the present study were to develop a controlled-release bilayered tablet of aceclofenac (AFN) 200 mg with dual release and to gain a mechanistic understanding of the enhanced sustained release capability achieved by utilizing a binary mixture of the sustained release materials. Different formulations of the sustained-release layer were formulated by employing hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) as the major retarding polymers. The in vitro dissolution studies of AFN bilayered tablets were carried out in intestinal fluid (pH 6.8 buffer). The mechanism of the synergistic rate-retarding effect of the polymer mixture containing HPC and carbomer was elucidated by the rate of swelling and erosion in intestinal fluid and the molecular interactions in the polymer network. The optimized bilayered tablets had similar in vitro dissolution profiles to the marketed tablet Clanza®CR based on the similarity factor (f2) in combination with their satisfactory micromeritic, physicochemical properties, and stability profiles.

Highlights

 

• The optimized HPMC-based and HPC-based bilayered tablets had similar dissolution profiles to the marketed tablet Clanza^®CR.
• A dramatic increase of water uptake and a reduction of weight loss were observed in tablet containing the polymer mixture.
• Carbomer was the main component of the gel layer at initial stage, followed by a gradual transition of HPC to the gel layer.
• FT-IR spectra depicted a strong hydrogen bonding between HPC and carbomer in the polymer mixture.

Drug release from HPMC-based matrix was controlled by non-Fickian transport, while drug release from HPC-based matrix was solely governed by drug diffusion. The swelling and erosion data exhibited a dramatic increase of water uptake and a reduction of weight loss in the polymer mixture-loaded tablet. Fourier transform infrared (FTIR) spectra revealed strong hydrogen bonding between HPC and carbomer in the polymer mixture. Regarding spatial distribution of polymers in the polymer mixture-loaded tablet, carbomer was found to be the main component of the gel layer during the first 2 h of the hydration process, which was responsible for retarding drug release at initial stage. This process was then followed by a gradual transition of HPC from the glassy core to the gel layer for further increasing gel strength.

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