[Comparison of the Pharmaceutical Characteristics of Brand-name and Generic Pramipexole Extended-release Tablets and Their PTP Usability].

The pramipexole extended-release (long acting) tablet, a D2 receptor agonist commonly used for the treatment of Parkinson's disease, has increasingly demonstrated usability for patients with long acting performance and patient adherence improvements. As a generic drug it is sold by six companies while a brand name drug is also marketed. As these formulations are hygroscopic it is described as such in package inserts so that tablets will only be removed from the press-through package (PTP) immediately before ingestion. It is often dispensed in one-dose packaging (ODP) as determined by a patient's physical functions and symptom characteristics. With ODP, quality control and ease of removal from the PTP are important factors. In this study we examined the stability of tablets in the ODP (25℃ RH75%) while also comparing the ease of handling of the seven products currently marketed in Japan. In the tablets' ODP, changes such as swelling and decreases in tablets hardness were observed in six formulations. Differences were found among the products in comparison of packaging material, required tablet extrusion strength, and ease of removal. Given the differences in PTP materials and hygroscopicity it is suggested that pharmacists must not only consider the drug formulations of products but also contribute to improvements in medication adherence for patients with poor hand-finger function.

Drug Release Profiles and Disintegration Properties of Pectin Films.

We assessed the disintegration profiles of the film dosage forms (FDs) prepared using pectin by measuring the amount of pectin dissolved from the films in a limited amount of aqueous medium. Furthermore, we used miconazole and dexamethasone as standard drugs and investigated the relationship between the disintegration rate of the FDs and the rate of drug release. We used two types of pectin in this study to develop thin films with a thickness of approximately 25⁻35 µm. The FDs gradually disintegrated in the aqueous medium, and the disintegration profile of the FDs differed depending on the types of pectin. In addition, the rate of disintegration of the film matrix affected the dissolution rate of the drug incorporated into the FD. Thus, our results show that FDs prepared using pectin are beneficial because of their high solubility in a limited amount of medium, and the rate of drug release from the FDs can be regulated by selecting a specific type of pectin or by altering the concentration of the film base.

Control of Drug Dissolution Rate from Film Dosage Forms Containing Valsartan.

Film dosage forms (FDs) containing valsartan (VST), a popular antihypertensive drug, were prepared using a casting method with sodium alginate and other polysaccharides as the film base. Drug dissolution profiles of the FDs were investigated in limited medium. The FDs were 170-200 µm thick and were easy to handle. All FDs immediately swelled and disintegrated in the medium. About 23% of the VST incorporated into the FD prepared with 1.5% sodium alginate dissolved at 5 min. The initial dissolution rate of VST increased upon the addition of chitosan to the film base; this effect was not observed in the case of chitin. On the other hand, the rate apparently decreased upon modification with alginic acid. In addition, the solubility of VST in the dissolution medium was changed by the addition of chitosan or alginic acid. FDs prepared with polysaccharides are useful for simplifying the administration of drugs to patients, and the drug dissolution rate from FDs can be controlled by modification.

[Property of metronidazole film prepared with natural polysaccharides].

Film dosage forms containing metronidazole (MZ) were prepared from natural polysaccharides, such as pullulan (PUL) or sodium alginate (ALG), without heating or controlling the pH. The release profiles of MZ from the films were investigated. In the absence of a drug, the casting method resulted in the polysaccharide forming a circular film, and the presence of MZ affected film formation. The thickness of the film was controllable by adjusting the concentration of ALG, and regular unevenness was observed on the surface of film. The film prepared with PUL or ALG readily swelled in dissolution medium, and released MZ with disintegration. The films prepared from the polysaccharides could be promising candidates as dosage forms containing MZ, and would be expected to show drug dissolution in the surface of skin.

Effect of imatinib mesilate on the disposition kinetics of ciclosporin in rats.

The purpose of this study was to investigate the effect of imatinib mesilate on the disposition kinetics of ciclosporin in rats. The blood concentration-time course and pharmacokinetic parameters of ciclosporin did not significantly change after intravenous injection of ciclosporin (10 mg kg(-1)) in rats treated with imatinib mesilate (50 mg kg(-1)) as compared with a control. When ciclosporin (10 mg kg(-1)) was orally administered, the time course, area under the curve, bioavailability and peak blood concentration of ciclosporin were significantly increased in rats that had been treated with imatinib mesilate 2 h before ciclosporin administration as compared with the control. Because both drugs are transported via P-glycoprotein and breast cancer resistance protein and metabolized by cytochrome P450 3A2, the interaction of imatinib mesilate with these proteins may be responsible for the increased intestinal absorption of ciclosporin in rats. These results indicate that imatinib mesilate enhanced the intestinal absorption of ciclosporin in rats with only the oral administration of ciclosporin, suggesting that our results support clinical data. In addition, imatinib mesilate may increase the pharmacological effects and possibly toxicity of ciclosporin.