How to photostabilize molsidomine tablets.

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.

Particular features of photolabile substances in tablets.

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.

ICH guideline for photostability testing: aspects and directions for use.

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.

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.

Endoluminal treatment of infrarenal aortic aneurysms: clinical experience with the Talent stent-graft system.

PURPOSE: To evaluate the safety and efficacy of the Talent stent-graft (TSG) system in the endoluminal treatment of infrarenal abdominal aortic aneurysms (AAAs). PATIENTS AND METHODS: Endoluminal treatment of an AAA was attempted in 30 men with a mean age of 70.5 years (range, 51-83 years). Seven patients had AAAs suitable for treatment with a tube graft. In the other patients, treatment with a bifurcated TSG was planned. All procedures were performed as a combined surgical-radiologic procedure in an angiographic room. RESULTS: Primary technical success was achieved in 25 of 30 patients (83%). Technical failures were due to misplacement of the TSG (n = 2) with proximal leakage as a consequence, inability to gain access via the iliac arteries (n = 1), and a distal leakage (n = 2). Secondary interventions (n = 2) and spontaneous thrombosis of a distal leak (n = 1) increased the secondary technical success rate to 93% (28 of 30). Two procedures were converted to open surgery (conversion rate = 6%). One patient died during the first 30 days after uncomplicated stent-graft insertion because of myocardial infarction (30-day mortality = 5%). No complications occurred during a mean follow-up of 15.4 months (range, 6-19 months). The maximum diameter of the AAA decreased in eight patients and remained unchanged in the remaining patients. No increase in diameter was observed. No late endoleak or migration of the TSG was observed. CONCLUSION: The TSG-system revealed satisfactory initial and early follow-up results. Treatment of AAAs with this stent-graft system is feasible. The technical success rate in carefully selected patients should be 90% or more. However, long-term observations are necessary to determine if the encouraging early results of this type of therapy can be preserved during long-term follow-up.

[Endoluminal therapy of infrarenal aortic aneurysms with the Talent system--initial experiences with a new endoprosthesis]. / Endoluminale Therapie infrarenaler Aortenaneurysmen mit dem Talent-System--Erste Erfahrungen mit einer neuen Endoprothese.

PURPOSE: To report the early clinical experience with the Talent stent-graft system in the treatment of infrarenal aortic aneurysms. MATERIALS AND METHODS: The study group comprised 15 males aged from 51-79 years. A bifurcated Talent stent-graft was implanted in 9 patients with type B or C aneurysms, a tube graft in 6 patients with a type A aneurysm. The stent-grafts were introduced via a surgical femoral cut-down, for a bifurcated graft a bilateral surgical access was needed. All procedures were performed as teamwork by radiologists and vascular surgeons under general anaesthesia in the angiography suite. RESULTS: Primary and secondary technical successes were 80 and 86%, respectively. Technical failures were due to access site problems (n = 1; elective open repair), malpositioning of the prosthesis (n = 1; immediate conversion to open surgery), and primary distal leakage (n = 1; elective occlusion by means of distal stent-graft extension). One patient died 15 days after an uneventful stent-graft insertion (30-day mortality 6%). No complications were observed during a mean follow-up period of 7.8 months. The aneurysmal diameter decreased in 6 patients and remained unchanged in the others. CONCLUSIONS: The Talent system revealed satisfactory early results which are comparable to competitive stent-graft systems. An advantage of this stent-graft device is the availability in a wide range of dimensions. A major disadvantage is the large introducer system (french size 22-27).