EFFECTS OF FORMULATION PARAMETERS ON PROPERTIES OF GASTRIC FLOATING TABLETS CONTAINING POORLY SOLUBLE DRUG: DICLOFENAC SODIUM


Sitha Kim, Ekapol Limpongsa, Napaphak Jaipakdee

Abstract


Objective: The objective of this study was to prepare and investigate the effects of formulation parameters on the properties of gastric floating tablets containing diclofenac sodium (DICL) as a model of poorly soluble acidic drug, sodium bicarbonate (NaHCO3) or calcium carbonate (CaCO3) as gas-forming agent, hydroxypropyl methylcellulose (HPMC) K100M or K15M as swelling polymer and sodium lauryl sulfate (SLS) as wetting agent.

Methods: DICL floating tablets were prepared using direct compression method. The compressed tablets were evaluated for tablet properties, swelling index, and in vitro buoyancy. The in vitro release under non-sink condition was determined. Molecular interaction was studied using differential scanning calorimetry and fourier transform infrared spectroscopy.

Results: The tablet properties of all DICL floating tablets were within the acceptance criteria. The molecular interaction between DICL and excipients in the formulation was excluded. Depends on the formulation compositions, the swelling index at 3 h (SI) ranged from 44±11 to 1158±33 %, whereas the buoyancy properties namely floating lag time (FLT) and total floating time (TFT) were 0.33±0.03 to 10.04±0.04 min and 10.0±0.0 to>12 h, respectively. NaHCO3 showed higher swelling, buoyancy and release properties compared to those of CaCO3. NaHCO3 at 20% gave sufficient swelling (SI of 1074±16 %), buoyancy (FLT of 0.39±0.03 min, TFT of>12 h) and release properties (cumulative release of 5.83±0.02 %). HPMC K100M showed better swelling property of which its initial swelling rate was 1412±25 %/h compared to HPMC K15M (1042±31 %/h). HPMC K100M at 20% showed better buoyancy and release properties compared to those obtained from HPMC K100M at 30%. The release testing under non-sink conditions was able to distinguish the effect of formulation parameters on the DICL release profiles. Incorporation of SLS at 0.25% could enhance both release rate and cumulative release of DICL from the floating tablets. Nevertheless, it showed the unacceptable adverse effect on swelling and buoyancy properties of DICL floating tablets. The TFT of DICL floating tablets containing 0.25% SLS was only 0.5±0.0 h.

Conclusion: DICL floating tablets were successfully prepared. Tablets possessing suitable swelling and buoyancy properties were obtained using NaHCO3 at 20% as a gas-forming agent, with HPMC K100M at 10 and 20% as floating matrix and swelling polymer. Addition of SLS as wetting and solubilizing agent showed the unacceptable adverse effect on the swelling and buoyancy properties of DICL floating tablets. The release under sink conditions and/or in vivo pharmacokinetic studies shall be further performed.


Keywords


Diclofenac sodium, Floating tablet, HPMC, SLS

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