| Oral osmotic pump tablet holds a prominent place among controlled release preparations. Osmotic pressure was used as the driving force and a zero-order release rate was the delivering characteristic. The release rate of oral osmotic pump tablet was pH-independent and agitation-independent which leaded to similarity in vitro/in vivo, therefore reduced risk of adverse reactions, improved compliance of patients and exhibited comparable in vitro/in vivo drug release. Monolithic osmotic pump tablet was given more attention due to simplicity in preparation. In this study, the monolithic osmotic pump tablets of atenolol and oleanolic acid were prepared with a solubility-modulated method and solid dispersion technology, respectively.Atenolol is sparingly soluble in water, therefore it is not suitable for preparing elementary osmotic pump tablet. Tartaric acid was used as solubility-modulator and the soluble-ability of atenolol was enhanced significantly by acid-alkali reaction. Sodium chloride was used as osmotic agent and polyethylene pyrrolidone (PVPK30) as retardant agent, and the core tablet was compressed by the punch with a needle. Ethyl cellulose was employed as semi-permeable membrane. The amount of tartaric acid, the amount of sodium chloride, the amount of PVPk30 and the thickness of membrane were selected as four factors. Various formulations were optimized by orthogonal design and evaluated by similarity factor (f2). The optimal formulation was obtained as follows: atenolol, 25.0 mg; tartaric acid, 32.1 mg; PVPk30, 64.3 mg; NaCl, 128.6 mg. The optimal thickness of membrane was 0.300 mm.The monolithic osmotic pump tablet of atenolol had been successfully prepared using tartaric acid as solubility promoter. The optimal osmotic pump tablet was able to deliver atenolol at the rate of approximate zero-order up to 24 h, independent on release media and agitation rate. The approach of solubility-modulated by acid-alkali reaction might be used for the preparation of osmotic pump tablet of other sparingly-soluble drugs with acid or alkaline groups.Oleanolic acid was a poorly water-soluble drug. A water-soluble polymer PVPk30 and a nonionic surfactant Tween80 were employed as a combined carrier to prepare ternary solid dispersion of oleanolic acid. Sodium chloride was used as osmotic agent and polyethylene oxide (PEO, Mr: 5×105) as suspending agent, ethyl cellulose as membrane to prepare the monolithic osmotic pump tablet of oleanolic acid with the solid dispersion. The osmotic pump tablet was optimized by orthogonal design and evaluated by similarity factor. The optimal formulation was obtained as follows: oleanolic acid, 30 mg; PVPk30, 30 mg; Tween80, 6 mg; NaCl, 103 mg; PEO (Mr, 5×105), 131 mg. The optimal thickness of membrane was 0.170 mm.The monolithic osmotic pump tablet containing ternary solid dispersion of oleanolic acid had been successfully prepared. The prepared osmotic pump tablet could deliver oleanolic acid at an approximately constant rate up to 24 h, independent on both release media and agitation rate. This method might be applied to other poorly water-soluble drugs for the preparation of monolithic osmotic pump tablet. |
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