ABSTRACT
Different methods of photostabilization are presented for the very light sensitive molsidomine tablets. The incorporation of photostabilizers such as light absorber or pigments into the tablets considerably improved the photostability. Nevertheless, photodegradation was still detected after 12 h of intense light stress. Pigments are superior to colorants or ultraviolet absorbers. The use of titanium dioxide needs to be considered carefully. Preblending the pigment with the drug substance is very helpful for taking full advantage of its photostabilizing properties. Surface-treated titanium dioxide with reduced photocatalytic activity was less suitable than untreated. That was due to a change of particle agglomeration and adhesion behavior, which was demonstrated by scanning electron microscopy pictures. However, only the protection of the tablets by a cover, either by blistering or film coating, gave a photostable drug product.
Subject(s)
Molsidomine/chemical synthesis , Molsidomine/radiation effects , Drug Stability , Lighting , Molsidomine/pharmacokinetics , Photochemistry , Tablets, Enteric-Coated , Ultraviolet RaysABSTRACT
Nifedipine and molsidomine tablets are extremely photolabile drug preparations, even at cool room light. Compared to solutions the light spectrum responsible for photodegradation is moved towards the long-wavelength range corresponding to the bathochromic shift of light absorption in the solid state. In the case of nifedipine tablets light up to 500 nm, especially the range between 400-420 nm, is degrading. Molsidomine tablets are affected only by ultraviolet light, but not by visible light. In both cases light penetrates less than 1 mm into the tablets. For nifedipine tablets the exact penetration depth could be determined due to the discolouration of the drug substance upon irradiation. It varied from 360 microm to 880 microm depending on the drug content. Since the decomposition products of nifedipine act as photostabilizers by spectral overlay, light penetration and photodegradation in nifedipine tablets are limited. The formation of gaseous and liquid decomposition products in molsidomine tablets enhances photodegradation. Changes of the tablet structure as well as dissolution and migration processes are discussed. Furthermore the degradation products donot photostabilize the drug substance due to the missing light absorption above 300 nm.
Subject(s)
Calcium Channel Blockers/administration & dosage , Calcium Channel Blockers/chemistry , Molsidomine/administration & dosage , Molsidomine/chemistry , Nifedipine/administration & dosage , Nifedipine/chemistry , Vasodilator Agents/administration & dosage , Vasodilator Agents/chemistry , Calcium Channel Blockers/radiation effects , Chemistry, Pharmaceutical , Chromatography, High Pressure Liquid , Drug Packaging , Drug Stability , Light , Molsidomine/radiation effects , Nifedipine/radiation effects , Photochemistry , Sunlight , Tablets , Ultraviolet Rays , Vasodilator Agents/radiation effectsABSTRACT
The ICH guideline Q1B for photostability testing gives guidance on the basic testing protocol required to evaluate the light sensitivity and stability of new drugs and products. The choice of the irradiation method, although complying with the guideline demands, may effect test results. High irradiances may shorten testing times, but can lead to enforcement of photodegradation, which was demonstrated for molsidomine tablets. The exposure to an artificial light source (xenon lamp) was compared and correlated to natural daylight. Suitable testing methods for nifedipine and molsidomine tablets were developed. Deviating from the guideline recommendations, the presentation of powder samples should be done in tiny aluminium pans, facilitating the test procedure, minimising the risk of falsified test results due to improper sampling and improving reproducibility. When using glass dishes for the presentation of tablets to photostability testing, they should be lined by e. g. aluminium foil to avoid influences of light reflected from the sample tray.
Subject(s)
Drug Stability , Pharmaceutical Preparations/standards , Photochemistry/standards , Calorimetry, Differential Scanning , Chromatography, High Pressure Liquid , Light , Molsidomine/chemistry , Molsidomine/radiation effects , Nifedipine/chemistry , Nifedipine/radiation effects , Sunlight , Tablets , Ultraviolet RaysABSTRACT
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.
