Formulation study for lansoprazole fast-disintegrating tablet. III. Design of rapidly disintegrating tablets.

Lansoprazole fast-disintegrating tablets (LFDT) are a patient-friendly formulation that rapidly disintegrates in the mouth. LFDT consist of enteric-coated microgranules (mean particle size, approximately 300 microm) and inactive granules. In the design of the inactive granules, mannitol was used as a basic excipient. Microcrystalline cellulose, low-substituted hydroxypropyl cellulose (L-HPC), and crospovidone were used as binders and disintegrants. A new grade of L-HPC (L-HPC-33), with a hydroxypropoxy group content of 5.0-6.9%, was developed and it has no rough texture due to a decrease in water absorption. It was clarified that L-HPC-33 could be useful as a binder and disintegrant in rapidly disintegrating tablets. LFDT contain enteric-coated microgranules in tablet form. The enteric-coated microgranule content in LFDT affect qualities such as tensile strength, disintegration time in the mouth, and dissolution behavior in the acid stage and in the buffer stage of LFDT. The 47.4% content of the enteric-coated microgranules was selected to give sufficient tensile strength (not less than 30 N/cm(2)), rapid disintegration time in the mouth (not more than 30 s), and dissolution behavior in the acid stage and buffer stage similar to current lansoprazole capsules. Compression force affected the tensile strength and the disintegration time in the mouth, but did not affect the dissolution behavior in the acid and buffer stages.

Testosterone 17beta-N,N-dimethylglycinate hydrochloride: A prodrug with a potential for nasal delivery of testosterone.

The purpose of this study was to examine the potential of the nasal route for the systemic delivery of the poorly water-soluble drug testosterone (TS) using a water-soluble prodrug, TS 17beta-N,N-dimethylglycinate hydrochloride. The physicochemical properties of the prodrug, in vitro hydrolysis in human liver homogenate, and in vivo nasal and intravenous experiments were performed in rats. The aqueous solubility of the prodrug was more than 100 mg/mL, compared with 0.01 mg/mL for TS, and its log partition coefficient between 0.05 M, phosphate buffer (pH 6) and octanol was 2.4. The prodrug was found to generate TS in 33% human liver homogenate and was absorbed from the nasal cavity rapidly and quantitatively. The bioavailabilities of both the prodrug and TS after nasal administration of the prodrug were similar to that after equivalent intravenous doses. These studies in rats suggest that this water-soluble prodrug of TS may have therapeutic utility for the management of TS deficiency.