Purpose: To enhance the dissolution rate of the poorly soluble drug ATORVASTATIN calcium (ATC) by cocrystallization with selected coformers. Enhancement of the dissolution rate and solubility of the drug, which is classified as Class II of the Biopharmaceutical Classification System (BCS), is expected to enhance the bioavailability. Methods: Two methods were used for preparing the cocrystals, solvent drop grinding (SDG) and solvent evaporation (SE) method using 1: 1, 1: 3, and 1: 10 drug-coformer molar ratios. Glucosamine hydrochloride (GluN) and nicotinamide (NIC) were investigated as coformers. The cocrystals, their physical mixtures, and the raw ATC were characterized by fourier transform infrared (FTIR spectroscopy), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), mass spectroscopy (MS), scanning electron microscopy (SEM), solubility, and dissolution rate studies. Results: SDG and SE were effective in improving the dissolution rate of ATC with both coformers. Drug: coformer ratio 1: 3 was optimum. The solubility values for ATC, GluN-, and NIC-cocrystals were 26, to 35 and 50 μ g/mL, respectively. The dissolution rate of ATC from cocrystals was > 90% after 5 minutes, compared to 41% untreated ATC. Conclusion: Cocrystallization significantly improved the solubility and dissolution, in comparison to the untreated ATC.

Background: Although the bio kinetics, metabolism and chemical toxicity of ATORVASTATIN are well known, until recently little attention was paid to the potential neurotoxic effect of ATORVASTATIN (Atv). Regarding the concrete evidences indicating Atv may reduce Coenzyme Q10 (CoQ10) levels through blockage of metalonate cycle, the present work aims to determine if ATORVASTATIN may provide toxic effects on brain mitochondria and whether its supplementation with two lipidicantioxidants, CoQ10 and Vit E may improve such outcomes. Methods: to evaluate mitochondrial toxicity, male NMRI mice were first treated with ATORVASTATIN(bo; 20 and 60 mg/kg) every other day with or without supplementation with CoQ10 (200 mg/kg) or Vit E (40 u/kg). After a period of 4 weeks, the animals were euthanized and brain cortices were harvested ad subjected to mitochondria isolation procedure. ROS release, mitochondrial membrane potential (MMP) and cytochrome c release were performed to precisely address the probable mitochondrial injury. Findings: Our data showed increased ROS formation, MMP collapse, mitochondrial swelling and cytochrome c release in ATORVASTATIN treated mice, suggesting that mitochondrial ROS formation and apoptosis signaling are likely involved in ATORVASTATIN neurotoxicity. Importantly according to the data from animals receiving either CoQ10 or Vit E, supplementation with these lipophilic antioxidants, remarkable reverted the corresponding ATORVASTATIN mitochondrial toxicity markers. Concusion: Conclusively the present work addresses chronic ATORVASTATIN toxic effects on brain mitochondria and supports advantages of Vit E or CoQ10 supplementation. Whether such neurotoxic effect is correlated with CoQ10 depletion or if the improving effects of the due supplementation contribute toATORVASTATIN receiving patients, needs more investigations.

Introduction: Cryopreservation is widely used in ART clinics for many different conditions such as; male problems. Sperm cryopreservation has some technical limitation and decreased sperm motility, viability and fertilization rate. Looking for new technique, drug or natural compound to improve sperm parameters after cryopreservation is under investigation. Statin family (HMG-CoA reductase inhibitor) is widely used as cholesterol lowering and decreasing cardiovascular mortality and morbidity. Attention to these drugs is increasing nowadays. ATORVASTATIN, a member of statin family shows anti-inflammatory, anticancer and endometriosis treating effects. The aim of present work is to investigate the effect of ATORVASTATIN on mouse sperm motility, viability after cryopreservation.Materials and Methods: Epididymal spermatozoa, from adult NMRI mice, were collected into DMEM/F12 medium and incubated at 37oC for 30 minutes. Samples containing 1 ml of the cryoprotectant (18% rafinose and 3% skimmed milk in water) and stored in liquid nitrogen (-196oC). After one week, frozen samples were thawed rapidly by removing from liquid nitrogen storage and placed into a water bath at 37oC until all ice crystals are melted after approximately 2 minutes and divided into 4 groups (Control, 0.1, 1 and 10 mg/ml ATORVASTATIN). All the samples were assessed by WHO procedure (motility, viability and morphology). Data were statistically analyzed by one way ANOVA (p<0.05).Results: There was no significant difference between all control and case groups in sperm motility and viability after cryopreservation.Conclusions: ATORVASTATIN did not improve mouse sperm parameters after cryopreservation.