Color change in Perlodel® tablets induced by LED lighting - photolysis of bromocriptine mesylate.

Various types of fluorescent lights are found in the dispensing rooms of medical facilities, such as hospitals and pharmacies, in Japan. However, to reduce electric power consumption, it was necessary to evaluate the substitution of fluorescent lighting with light emitting diode (LED) lighting, which has become widespread in recent years. We subjectively evaluated several types of medicines stored under various light sources and found that different color changes were induced in tablets. In this study, we focused on Perlodel ® tablets, containing 2.5 mg bromocriptine mesylate, as an example for the objective evaluation of the differences in the color change of tablets when stored under LED lighting and fluorescent lighting. High-performance liquid chromatography (HPLC) analysis of part of the tablet surface area revealed a change from white to light brown or dark brown after 28 days of irradiation, with a residual concentration of bromocriptine mesylate of 85.5 % under fluorescent lighting, 85.6 % under daylight-color LED lighting, 90.3 % under bulb-color LED lighting, and 99.2 % in the dark. In addition, the ultraviolet (UV)-visible spectral study of the absorbance of a photo-product at 400-550 nm indicated that the color change of the Perlodel® 2.5 mg tablet was caused by photochemical degradation of bromocriptine mesylate. Thus, this analysis of the photochemical changes in drugs stored under different light sources demonstrated the potency of LED lights. Through the objective evaluation of the color change, the cause of the color change was determined; this will allow us to develop a strategy that minimizes possible disadvantages to patients, such as a decrease in treatment efficacy owing to decomposition of the main component or adverse caused by decomposed matter.

Preparation of Orally Disintegrating Tablets Containing Powdered Tea Leaves with Enriched Levels of Bioactive Compounds by Means of Microwave Irradiation Technique.

In the present study, a microwave treatment process has been applied to prepare orally disintegrating tablets (ODTs) containing powdered tea leaves with enriched levels of the anti-inflammatory compounds such as chafuroside A (CFA) and chafuroside B (CFB). The use of distilled water as the adsorbed and granulation solvents in this preparation process afforded tablets with a long disintegration time (more than 120 s). The CFA and CFB contents of these tablets did not also change after 4 min of microwave irradiation due to the tablet temperature, which only increased to 100°C. In contrast, the tablet temperature increased up to 140°C after 3 min of microwave irradiation when a 1.68 M Na2HPO4 solution instead of distilled water. Notably, the disintegration time of these tablets was considerably improved (less than 20 s) compared with the microwave-untreated tablets, and there were 7- and 11-fold increases in their CFA and CFB contents. In addition, the operational conditions for the preparation of the tablets were optimized by face-centered composite design based on the following criteria: tablet hardness greater than 13 N, disintegration time less than 30 s and friability less than 0.5%. The requirements translated into X1 (the amount of granulation solvent), X2 (tableting pressure) and X3 (content of the powdered tea leaves) values of 45%, 0.43 kN and 32%, respectively, and the ODTs containing powdered tea leaves prepared under these optimized conditions were found to show excellent tablet properties and contain enriched levels of CFA and CFB.

Design and evaluation of microwave-treated orally disintegrating tablets containing polymeric disintegrant and mannitol.

Microwave (MW) treatment was used to develop a formulation process for the preparation of wet molded orally disintegrating tablets (ODTs) consisting of mannitol and polymeric disintegrant with improved hardness and disintegration properties. The wet molded tablets were prepared in accordance with the conventional methods and subsequently heated by MW irradiation to induce the swelling of the tablet. Croscarmellose sodium, crospovidone, and low-substituted hydroxypropylcellulose (L-HPC) were evaluated for their use with this technology. NBD-020, which is a grade of L-HPC, provided the better hardness and disintegration results. In addition, the crystalline forms of mannitol impacted on hardness and disintegration properties of the ODT upon MW irradiation. The effects of the disintegrant ratio, δ and ß crystalline mannitol ratio, amount of water, and compression force on the ODT properties were evaluated using the design of experiment method. MW-induced swelling was enhanced by an increase in the disintegrant ratio. Although the hardness of the tablet increased following MW treatment, the disintegration time became less than that of the MW-untreated tablets as the ß-mannitol ratios increased. Taken together, the results indicated that the polymeric disintegrant greatly improved the properties of the molded tablets in combination with MW treatment.

Ultrasound-assisted powder-coating technique to improve content uniformity of low-dose solid dosage forms.

An ultrasound-assisted powder-coating technique was used to produce a homogeneous powder formulation of a low-dose active pharmaceutical ingredient (API). The powdered particles of microcrystalline cellulose (MCC; Avicel® PH-200) were coated with a 4% m/V aqueous solution of riboflavin sodium phosphate, producing a uniform drug layer on the particle surfaces. It was possible to regulate the amount of API in the treated powder. The thickness of the API layer on the surface of the MCC particles increased near linearly as the number of coating cycles increased, allowing a precise control of the drug content. The tablets (n = 950) prepared from the coated powder showed significantly improved weight and content uniformity in comparison with the reference tablets compressed from a physical binary powder mixture. This was due to the coated formulation remaining uniform during the entire tabletting process, whereas the physical mixture of the powders was subject to segregation. In conclusion, the ultrasound-assisted technique presented here is an effective tool for homogeneous drug coating of powders of irregular particle shape and broad particle size distribution, improving content uniformity of low-dose API in tablets, and consequently, ensuring the safe delivery of a potent active substance to patients.

The influence of formulation and manufacturing process on the photostability of tablets.

The formulation and the manufacturing process can significantly influence the photostability of tablets. Investigations of various formulation and manufacturing parameters were done with tablets containing nifedipine and molsidomine as highly light sensitive drugs. The effect of relevant formulation factors are stated. Whereas the particle size of the drug substance and the choice of the lubricant had no effect, the drug content, the compression diluent and geometric alterations significantly affected the photoinstability. Depending on the formulation drug losses varied between 30 and 55% after 12 h irradiation in a light testing cabinet (Suntest CPS+). Manufacturing parameters like compression force and direct compression versus granulation showed less serious influences. Nevertheless, photostability changes up to 10% were registered.

Influence of neutron activation factors on matrix tablets for site specific delivery to the colon.

The impact of the neutron activation procedure, i.e. incorporation of samarium oxide (Sm(2)O(3)) and neutron irradiation, on the compression properties (including the crushing strength) and in vitro dissolution of potential colonic delivery systems based on matrix tablets of amidated pectin (Am.P) or two types of hydroxypropyl methylcellulose (HPMC) was investigated. The neutron activation factors did not influence the compression properties of the tablets. Replacement of magnesium stearate with samarium stearate in directly compressed Am.P tablets to achieve both radiolabelling and lubrication resulted in a greater extent of concentration-dependent reduction of the crushing strength. Dissolution tests demonstrated that irradiation increased the release of the model drug ropivacaine from the tablets. The extent of this increase was unexpectedly low considering the previously observed degradation of the polymer expressed as an irradiation-induced viscosity reduction in solutions prepared from the polymers. Delayed-release coating with Eudragit L 100 protected the HPMC tablets against the release-increasing effect of irradiation until the late phases of release. Sm(2)O(3) retarded the release to a varying extent depending on particle characteristics. Incorporation of Sm(2)O(3) in the coating layer did not influence the release. However, one-third of the radioactivity leached from the coating within 60 min in 0.1 M HCl.