Rifampicin (RIF) is a first-line antitubercular (anti-Tb) drug despite its decreased oral bioavailability and remarkable hepatotoxicity owing to its poor aqueous solubility. A coconut oil-based RIF-loaded self-nanoemulsifying drug delivery system (RF1) was developed beforehand to resolve the solubility issue. This work aimed to appraise the pharmacokinetic (PK) profiles and safety properties of RF1 for future endeavors. The comparative PK and safety profiles of pure RIF and the RF1 formulation were elucidated after oral administration to Wistar rats. In the PK study, blood sample was collected at definite time intervals from experimentally grouped animals orally administered raw RIF or RF1 at dose of 50 mg/kg body weight (b.w.). For the safety study, pure RIF and formulated RF1 were administered consecutively for fourteen days, dosed 50 and 125 mg/kg b.w. Twenty-four hours after final dose, the blood, liver, and kidney samples were amassed for biochemical analysis and histological characterization. RF1 revealed a 1.5-fold greater relative bioavailability (F) and a 1.4-fold greater Cmax within 30 min (Tmax) than did raw RIF, resulting in an improved AUC0-480 of RF1, with a comparable mean residence time and elimination half-life of the drug, indicating its potential pharmacological efficacy. Moreover, the in vivo safety evaluation revealed RF1 as innocuous as pure RIF, as characterized by liver and kidney markers and corresponding histological observations. Based on the findings from PK and safety studies, the SNEDDS of RIF might be a potential alternative for delivering rifampicin orally and may improve bioavailability while minimizing toxicity.

The aim of present investigation was to develop self-nanoemulsifying drug delivery system of rifampicin (RIF) using vegetable oils for improved drug release and tuberculostatic activity (TSA). A number of lipid-based formulations were developed using vegetable oils, polysorbate 80, and ethanol at different weight ratio. The formulations were optimized based on visual assessment, in vitro dissolution study, electro-physical characterization and transmission electron microscopic analysis. The optimized formulation was subjected to in vitro TSA study against two clinically RIF-sensitive strains of M. tuberculosis (Mtb) followed by accelerated stability evaluation. Visual observation ascertained the self-emulsification efficiency of all the emulsions (NEs) in terms of clarity, homogeneity, and phase separation. Dissolution study of RIF-loaded NEs revealed that complete (100%) drug release was obtained by RIF-NE7 within 45 min, whereas pure drug liberated maximum 59.6%. This enhanced drug release was attributed to self-nanoemulsification accomplished through its globule size (GS), poly dispersity index (PDI) and zeta potential (ZP) by 230.2 nm, 0.768 and -79.2 mV, respectively. The in vitro TSA study revealed that the dissolution samples of RIF-NE7 at 30 and 45 min were capable to inhibit the growth of Mtb strains, while pure RIF showed no inhibition till 120 min. Finally, the accelerated stability study indicated no significant variation of RIF-NE7 in aspect to its drug release pattern, GS and ZP. Observation of this study conferred that the newer lipid-based formulation would be a promising alternative to conventional rifampicin therapy to combat tuberculosis.

Azithromycin possesses low aqueous solubility leading to inadequate absorption and poor bioavailability after oral administration. Solid dispersion of azithromycin represented a formulation with enhanced dissolution and antibacterial activity. The study designed to evaluate the in-vivo potential of azithromycin-loaded solid dispersion in Escherichia coli-induced diarrheagenic (DEC) mice. Diarrhea was induced in Swiss Albino mice by the oral administration of bacterial culture (100 μl of 1010 CFU/ml) in high glucose Dulbecco’s modified Eagle’s medium (DMEM). The E. coli-infected diarrheal mice received oral administration of azithromycin-loaded solid dispersion, equivalent doses of pure azithromycin and/or vehicle (DMEM in high glucose) for 3 days; and their effects on diarrheal score, inflammatory markers, and histology of intestinal tissues were observed. Azithromycin-loaded solid dispersion treatment prevented diarrhea and retardation of growth in infected mice more efficiently than the equivalent doses of pure azithromycin. The E. coli-infected mice demonstrated soft feces with irregular intervals; however, the nature and frequency of feces were improved with azithromycin-loaded solid dispersion. The increased level of total white blood cells and % of neutrophil was also significantly decreased with solid dispersion of azithromycin. In contrast, pure azithromycin did not alter the counts compared to disease control mice. Furthermore, the colonic tissues of E. coli-infected mice showed loss of epithelial integrity with sub-mucosal edema and also associated with increased serum amylase and C-reactive protein levels. However, solid dispersion of azithromycin-treated mice exhibited restoration of colonic tissue structure with a significant attenuation in serum amylase and C-reactive protein levels compared to pure azithromycin and/or vehicle-treated mice. Solid dispersion of azithromycin was more effective against E. coli-infected diarrheagenic mice than the equivalent doses of pure azithromycin; and the effect was dose-dependent. J. Bio-Sci. 32(1): 69-82, 2024

Cefuroxime Axetil (CA) a widely used cephalosporin antibiotic displays low aqueous solubility and high membrane penetrability. This results in its solubility driven variable and/or low oral bioavailability and therapeutic efficacy as a major drawback. Thus, most of the goal of our study was to increase the solubility as well as dissolution rate of CA using the simple and cost-effective solid dispersion (SD) method. At first, the SD formulations of CA were prepared at various weight ratios of Carplex-67 and PEG-4000 by solvent evaporation technique. These new formulations were then subjected to an in-vitro drug release performance study and tested for physicochemical characterization to distinguish the thermal behavior, crystallinity, interactions phenomena, and surface morphology. Among the formulated Cefuroxime Axetil Solid Dispersion (CSD), CSD-8 which contained CA, Carplex-67, and PEG-4000 at the weight ratio 1:3:2, respectively showed the most significant (p in-vitro dissolution in water, Gastric Simulated Fluid (GSF), and Intestinal Simulated Fluid (ISF). This study also showed a significant (p < 0.001) increase in drug release compared to the marketed product. Therefore, it is supposed to be a promising alternative to conventional antimicrobial therapy.

Abstract Objectives In this study, our main objective was to estimate the therapeutic effectiveness of the formulated solid dispersion of glibenclamide (GSD) with improved dissolution profiles in comparison with pure glibenclamide (GLB) by means of a fructose-fed diabetic rat model. Methods To evaluate the pharmacological effectiveness of the formulated GSD, a fructose-fed diabetic rat model evolved and the obtained consequences were compared with the conventional GLB treatment. Key findings GSD exhibited improved glucose and lipid-lowering efficacy of GSD in contrast to pure GLB after 15 days of treatment. Low dose (0.5 mg/kg) and high dose (5 mg/kg) of GSD showed significant lowering of blood glucose which is 6 ± 0.2 mmol/L and 5.6 ± 0.3 mmol/L respectively after 15 days of treatment is much better than that of pure GLB (6.2 ± 0.4 mmol/L). Furthermore, low dose of GSD presented approximately comparable beneficiary effects in regard to triglycerides (72.00 ± 7.23 mg/dL), total cholesterol (110.33 ± 5.78 mg/dL), low-density lipoprotein (67.60 ± 5.21 mg/dL) and high-density lipoprotein (28.33 ± 1.53 mg/dL) as pure GLB after 15 days. Additionally, histological studies as well confirmed no fatty infiltration from the liver by GSD as compared with GLB which was consistent with the biochemical parameters. Conclusions For treating diabetes and hyperlipidaemia, the formulated GSD might be a potential substitute for traditional GLB.

Paracetamol (PCM) is enlisted in the WHO model list as an essential medicine for pain and palliative care, but at overdose, it causes hepatic damage. This study was designed to assess the analgesic efficacy and hepatoprotective property of a solid dispersion (SD) loaded with PCM. A number of PCM loaded formulations (PSDs) were fabricated using silica alone or in combination with polyethylene glycol and/or Na-citrate followed by in-vitro dissolution profiling. Selected PSDs with improved dissolution profile were subjected to solid-state characterization (DSC, PXRD, FTIR, and SEM), stability study along with investigation of in-vivo analgesic efficacy and effect on hepatocytes. Among these, PSD10 showed a rapid and significantly higher in-vitro drug release than pure PCM. This improvement was distinct to other PSDs also. Solid-state characterization of PSD10 authenticated the conversion of crystalline PCM to amorphous form upon formulation. Subsequent oral administration of PSD10 in Swiss albino mice showed 1.44-fold greater analgesic efficacy than pure PCM at dose 30 mg/kg. Besides, at acute toxic dose, liver histology of PSD10 mice was comparable with NC mice indicating hepatic protection upon formulation, whereas the PCM mice showed extensive hepatic necrosis which was also endorsed by significantly higher values of SGPT, SGOT, and ALP than PSD10 mice. Finally, an accelerated stability study of PSD10 performed according to the guideline of ICH noticed no remarkable deviation in its dissolution performance as well as crystalline nature. Thus, this newly developed PSD10 may be a safe and promising alternative for pain management and palliative care.

Aim: Aqueous solubility of drugs is a determining factor for bioavailability in systemic circulation and confronts in the unbeaten formulation of therapeutic agents. Cefuroxime axetil (CA) is a broad-spectrum P-lactamase cephalosporin that pertains to class II drugs under Biopharmaceutical Classification System (BCS) with poor aqueous solubility and high absorption permeability after oral administration. The objective of this current work was to achieve the enhanced solubility in water and subsequent antibacterial activity of CA loaded coarse dispersion (CCD) formulations. Materials and Methods: CCDs were prepared by anti-solvent precipitation method by blending CA with a carrier, Microcrystalline cellulose (MCC) at different ratios. In-vitro dissolution test using paddle method and antibacterial study against Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922) were carried out for both pure CA and CCDs for performance comparison. Results: Among the formulations, CCD-3 exhibited maximized dissolution rate by 1.67-fold higher than that of pure CA with the drug-carrier (CA: MCC) ratio of 1:3. Antibacterial activity of CCD-3 against S. aureus and E. coli was also found by 1.75-fold and 5.25-fold higher relative zone of inhibition (RZ01), respectively than that of pure drug. Conclusion: As an optimized formulation, CCD-3 is a promising to be a fruitful substitute to conventional dosage forms of CA for the modified dissolution rate and antibacterial potency. However, before its recommendation as a novel formulation validation study to point its pharmacokinetics, competence with in-vivo antibacterial property and safety is needed.

Introduction: Dental caries is one of the most prevalent and chronic oral diseases, particularly in childhood, associated with multifactorial causation. Objective: The study aimed to determine the prevalence of dental caries, oral hygiene status, and associated risk factors among school-going children of Rajshahi District in Bangladesh. Methods: This cross-sectional design type of descriptive study was carried out among primary school-going children of 5-13 years of age in the Rajshahi district. The sample size was 2000, and that was selected purposively. Data were collected through a partially structured questionnaire. Descriptive variables were explained with mean and standard deviation. The Chi-square test was applied to see the relationship with qualitative variables. Statistical significance was found by applying relevant statistical tests at an appropriate probability level (p<0.05 or <0.01). Results: A total of 2000 children between 5-13 years of age participated in this survey. The study findings showed a high prevalence of dental caries among 8–10-years old school children. Most (56.9%) of the respondents' fathers were workers, and most (86.3%) of the respondents' mothers were homemakers. It was found that 64.2% of the respondents' fathers and 74.05% of the respondents' mothers had below SSC level of education. About 60% of the respondents brushed their teeth twice a day, and a good number (81.0%) brushed their teeth before breakfast. The majority (68.80%) of the respondents had a family history of dental problems, and 45.6% had average oral hygiene. A large number (49.6%) of the respondents' favorite food was junk food. The relationship of age of the respondents with oral hygiene status was found to be statistically significant (p <0.001) but not with sex, parents' education, and occupation (p >0.05 each). The relationship of oral hygiene status of the respondents was found to be statistically significant with the frequency of tooth brushing (p <0.05), time of tooth brushing (p <0.01), family history of dental problems (p <0.05), most favorite food (p <.001), dental plaque index (p <0.001) and dental caries index (p <0.001). Conclusions: The prevalence of dental caries was higher among school-going children in the Rajshahi district of Bangladesh. TAJ 2022; 35: No-1: 125-136

The study was designed to evaluate the safety and efficacy of cilnidipine (CLN) and Mg-supplementation in fructose-induced diabetic rats. Diabetes was induced into male Wister rats by feeding fructose (10% solution) in drinking water for 8 weeks. Diabetic rats were subjected for the oral administration of CLN1 (1 mg/kg/day) and CLN10 (10 mg/kg/day), and/or methyl cellulose (0.5%) as vehicle for 28 days. After 14 days of CLN treatment, MgSO4 (1%) was added to CLN1 and CLN10 groups for another 14 days. Age-matched healthy rats were used as normal control. After 28 days body weights were measured and organ weight to body ratio was calculated. Serum samples were analysed for fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), uric acid, lipid profiles, tri-iodothyronine (T3) and thyroid stimulating hormone (TSH), serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), creatine phosphokinase myocardial-band (CK-MB), creatinine, albumin, electrolytes. Oral glucose tolerance tests (OGTT), liver histopathology and in-vivo antioxidant activities were also performed. The survival rate in diabetic rats was 100% after the oral administration of CLN, Mg-supplement and/or vehicle. A significant reduction in FBS levels and improvement in OGTT were observed in CLN10, CLN1+Mg and CLN10 + Mg groups after 28 days. Further, the treatment ameliorated serum lipid profile, uric acid, and albumin levels. The groups CLN10 and CLN10 + Mg improved HbA1c, liver glycogen, creatinine, T3, TSH levels and electrolytes in diabetic rats. Moreover, liver from CLN10 and CLN10 + Mg groups showed preservation of cellular architecture as evidenced by attenuation of inflammatory markers SGPT, SGOT and CK-MB; and the levels of superoxide dismutase (SOD), catalase (CAT), glutathione, malondialdehyde (MDA), markers of oxidative stress were significantly improved. CLN exerted prominent effects in the amelioration of hyperglycemia, dyslipidemia and reduced hepatic inflammation; and Mg-supplementation might have some beneficial effects on diabetic complications and oxidative stress in fructose-induced diabetic rats.

Aims: Glibenclamide is an oral hypoglycemic agent exhibits inadequate aqueous solubility resulting in poor and unpredictable bioavailability. The study was designed to enhance the solubility and dissolution of glibenclamide by solid dispersion. Place and Duration of Study: Department of Pharmacy, University of Rajshahi, Bangladesh between June 2017 and July 2018. Methodology: Solid dispersions of glibenclamide were prepared by solvent evaporation technique using mixture of PEG-8000, sodium citrate, HPMC as additives in different ratios and subsequently, in-vitro dissolution studies were performed. The characterization of solid dispersions was done by Differential Scanning Calorimetry, Powder X-ray Diffractometer, Fourier Transform Infrared Spectroscopy and Scanning Electron Microscope. Results: Out of twelve formulations, the GCHP-4 composed of glibenclamide: HPMC: Na-citrate: PEG-8000 1:1:1:1) demonstrated highest percentage of yield (87.76%) and encapsulation efficiency (95.68%). The maximum dissolution of glibenclamide obtained from GCHP-4 (3.34 µg/ml), which was 5.2-fold higher than that of pure glibenclamide (0.64 µg/ml) at 120 min. The mechanism of increased solubility of glibenclamide from solid dispersion might be resulted due to the conversion of its crystalline form into amorphous state and no interaction between drug and carriers which was confirmed by differential scanning calorimetry and fourier transform infrared spectroscopy respectively. Conclusion: The dissolution rate of glibenclamide was greatly increased when loaded in solid dispersions which might be responsible for the improvement of its bioavailability in aqueous medium.

Aim: Azithromycin (AZ) possess high permeability but low solubility in gastrointestinal (GI) fluid and exhibited unpredictable dissolution profile resulting in poor oral bioavailability. Therefore, the study was aimed to enhance the dissolution rate of AZ and evaluation of its in-vitro antibacterial activity. Materials and Methods: Solid dispersions of AZ (ASDs) were prepared by solvent evaporation technique using Na-CMC alone or in combination with Carplex-80 as carrier in different ratios. Subsequently, in-vitro dissolution study were performed followed by physicochemical characterization using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) and finally antibacterial activity were assessed. Results: The formulation ASD-6 exhibited faster (6.59% at 5 min) and higher (20.02% at 120 min) drug release which were 4.84 and 7.94 fold higher than that of pure AZ. A significant increase in relative zone of inhibition (RZOI) was observed with ASD6 (p<0.001) when compared to that of pure AZ against S. aureus and E. coli at each sampling point. Conclusion: The in-vitro dissolution study indicated that among the six formulations AZ: Carplex-80: Na-CMC (1:3:2) complexes prepared by solvent evaporation technique exhibited highest dissolution rate and which might be responsible for enhanced antibacterial efficiency.

This investigation was undertaken to enhance the solubility and consequent antibacterial activity of cefuroxime axetil (CA), a β-lactamase-stable broad spectrum second generation cephalosporin through solid dispersion (SD) technique.For this purpose, CA loaded SDs (CSDs) were prepared by solvent evaporation method using different concentrations of microcrystalline cellulose (MCC) as carrier.The CSDs were characterized by in-vitro dissolution study, thermal analysis (DSC), crystallinity (PXRD), interactions (FTIR) and morphology (SEM).Among the formulations, CSD-2 showed the highest dissolution rate which was 2.59-fold higher than pure CA with a drug-carrier (CA: MCC) ratio of 1:3.Enhanced dissolution rate was attributed to conversion of drug from crystalline to amorphous state during preparation of SDs, which was validated by DSC, PXRD, FTIR and SEM analyses.Antibacterial activity of CSD-2 against Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922) showed 1.94-and 6.75-fold higher relative zone of inhibition (RZOI), respectively than pure CA.CSD-2 has been found to be the most effective optimized formulation in terms of both enhanced dissolution rate and antibacterial activity.Thus, it can be an effective alternative to conventional dosage forms of CA.However, further investigations are needed to validate its pharmacokinetic properties, in-vivo antibacterial efficacy and safety before recommending as a novel formulation.

Exposures to hazardous chemicals including formaldehyde are harmful to human health. In this study, the authors investigate the protective effects of pumpkin seed oil (PSO) extract against formaldehyde-induced major organ damages in mice. Administration of formaldehyde (FA) caused significant elevation of serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum creatinine, etc. Histopathological examinations of liver, kidney, and brain tissues showed the degenerations of those organs. Mice pretreated with PSO extract significantly attenuated the FA-induced elevation of SGOT (39.0 ± 1.30 vs 20.5 ± 0.65 IU/L; FA-group vs PSO treatment group), SGPT (91.8 ± 1.65 vs 51.0 ± 1.29 IU/L), serum creatinine (1.05 ± 0.07 vs 0.65 ± 0.07 IU/L), and preserved the normal histology of organ tissues. The FA-induced elevation of malondialdehyde (MDA) in the brain, liver, and kidneys was suppressed by pretreatment with PSO extract. The extract also attenuated the FA-induced reduction of endogenous antioxidant pools. In vitro phytochemical analyses showed that PSO extract possesses free radical scavenging and total antioxidant activities due to the presence of phenolic and flavonoid compounds. Thus, PSO extract has significant protective effects against FA-induced organ toxicities by scavenging oxidative stress and inhibiting lipid peroxidation.

Probiotic bacteria with anti-inflammatory properties have the potential to be of therapeutic benefit in inflammatory bowel diseases. The present study was designed to evaluate the effect of feeding low-fat probiotic yogurt containing L. acidophilus and L. bulgaricus on acetic acid-induced inflammation in mouse colon. Inflammatory model that mimics various features of IBDs was induced by a single application of 100µl of 4.5% acetic acid in Swiss Albino mice. Mice were pretreated orally by 200µl yogurt containing both L. acidophilus and L. bulgaricus for 3 days before induction of inflammation and 200µl yogurt was given orally for a period of 7 days after acetic-acid induction. The body weight, food and water intakes, serum biomarkers, macroscopic and histopathological studies of colon tissues were performed to evaluate the anti-inflammatory effect. Combined administration of both strains prevented the damages of villous and crypts in colon epithelial cells and thus provides unique mucosal protective effects in experimental colitis. In conclusion, feeding low-fat probiotic yogurt containing L. acidophilus and L. bulgaricus prevented or ameliorated the inflammatory conditions that can be beneficial to prevent or lower risks of IBDs and its complications.

Objectives Hyperlipidaemia is a common phenomenon in diabetes mellitus. Fenofibrate (FF) is a good candidate for the treatment of lipid abnormalities in patients with type 2 diabetes. But the bioavailability as well as therapeutic efficacy of this drug is limited to its dissolution behaviour. Here, the authors assess the therapeutic efficacy of a newly formulated solid dispersion of fenofibrate (SDF) having enhanced dissolution profiles in contrast to pure FF using fructose-induced diabetic rat model. Methods Fructose-induced diabetic rat model was developed to assess the pharmacological efficacy of the formulated SDF, and the results were compared with the effects of conventional FF therapy. Key findings The 14 days treatment showed better improvement in lipid-lowering potency of SDF than pure FF. SDF containing one-third dose of pure FF showed similar effect in terms of triglyceride, total cholesterol and low-density lipoprotein lowering efficacy, whereas increased high-density lipoprotein at same extent. The similar dose of SDF produced more prominent effect than FF. Histological studies also demonstrated the enhanced lipid clearance from liver by SDF than FF that was concordant with the biochemical results. Conclusions This newly formulated SDF would be a promising alternative for conventional fenofibrate in treating hyperlipidaemia.

Fenofibrate (FF) is an anti-hyperlipidaemic drug belonging to BCS class-II (low solubility, high permeability).Its bioavailability is limited by the dissolution rate.This study was aimed to enhance the rate of dissolution of poorly water soluble drug, FF.Initially, solid dispersions of fenofibrate (SDFs) were formulated with Carplex-80 or PEG-4000 or in combination at various weight ratios and were subjected to dissolution study.On the basis of drug release at various time intervals, the formulation producing maximum drug concentration was evaluated physicochemically using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM).It was observed that the peak drug concentration was obtained at 120 min of dissolution by formulation SDF-7, which contains a mixture of Carplex-80 and PEG-4000 at weight ratio 1:5:6 of FF:PEG-4000:Carplex-80, respectively.Thus, the extent of drug release by SDF-7 was maximized by 2.5-fold than that of pure FF.Physicochemical characterization revealed the reason for this increased drug release as a conversion of crystalline FF to amorphous form and ensured the chemical compatibility among FF and carriers.The results specified the significant improvement of FF release using solid dispersion technique.

The main objective of this research is to conduct a comprehensive study for enhancing the aqueous solubility of poorly water soluble gliclazide using hydrophilic fumed silica particles (Aerosil® 380) and evaluating the influence of silica on drug release profile and pharmacological activity on alloxan induced diabetic rats. Solid dispersions (SD’s) of gliclazide were prepared using solvent evaporation method. The dissolution profiles and solid state characterization of the SD’s prepared were all evaluated. The dissolution rate of gliclazide in the SD’s with fumed silica (weight ratio, 1:1) was approximately 38%, which is about 10 fold higher than that of the pure drug after 30 min. After forming the SD’s, gliclazide changed into an amorphous state, which can infer from differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Fourier transform infrared spectroscopy (FTIR) also revealed the formation of weak hydrogen bonding through the interactions between the secondary amine groups of gliclazide and silanol groups of silica particles in the SD’s. The rapid dissolution rate from the SD’s might be attributed to the amorphization of drug, improved specific surface area and wettability than the original drug crystals. Further, we investigated the antidiabetic effects of SD’s of gliclazide in alloxan induced diabetic rats. The SD’s of gliclazide decrease the blood glucose level 64% whereas the conventional gliclazide decreases only 37% in diabetic rats. Lipid profiles, kidney and liver functions are remarkably improved in diabetic rat treated with SD’s of gliclazide than that of conventional gliclazide. These results suggest that SD’s of gliclazide have much more bioavailability and hence are more pharmacologically active than that of conventional gliclazide form.

Atorvastatin calcium (ATV) is a selective competitive inhibitor of HMG CoA reductase characterized by poor aqueous solubility leading to inadequate bioavailability. The present study was designed to develop solid dispersion of atorvastatin (SDA) to improve the solubility and dissolution properties of ATV and evaluation of its in-vivo efficiency in streptozotocin (STZ) induced diabetic mice. Formulations of SDA were prepared by solvent evaporation method using PEG-4000 alone and/or mixture of PEG-4000 and Carplex-80 as carrier in different ratios. Solid-state analyses of SDA were performed to characterize the physicochemical properties of newly developed SDA by differential scanning calorimetry (DSC), powder x-ray diffractometry (PXRD), fourier transformed infrared spectra (FTIR) and scanning electron microscopy (SEM). DSC and PXRD showed that the crystallinity of drugs was notably decreased during the preparation of SDA. FTIR and SEM also demonstrated the conversion of ATV from amorphous to crystalline state resulting in improved solubility. Among formulations, SDA-5 showed significant enhancement of in-vitro drug release (around 2 fold higher) as compared to pure ATV. Further, in-vivo study was conducted to evaluate the effects of a newly developed ATV loaded solid dispersion on glycemic control, lipid profile, liver enzyme and histopathology in STZ induced diabetic mice. Oral administration of SDA significantly lowered the blood glucose levels during the course of treatment. Treatment with SDA significantly improved lipid profiles better than ATV alone and the effect was dose-dependent. After one week of SDA treatment significantly decreased liver weights as result of lipid clearance and the hepatocytes regained their normal architecture, and these beneficial effects can be correlated with the reduction of SGPT levels. The results demonstrated that, SDA exerted better glycemic control, lipid lowering effect and organ protection (liver and pancreas) than that of conventional ATV in STZ induced diabetic mice. The mechanism by which SDA conferred better improvement in diabetic conditions can be partially explained by enhancement of solubility and dissolution rate when ATV is loaded in solid dispersion.

The use of Nifedipine (NI), a dihydropyridine calcium channel blocker, is limited due to its poor aqueous solubility.However, NI loaded solid-lipid nanoparticles (NI-SLN) are known to exhibit suitable pharmacokinetic properties and good biocompatibility.The present investigation was designed to evaluate the effects of NI-SLN on glucose homeostasis, lipid metabolism and liver function in fructose-induced diabetic rats.NI-SLN was prepared by high pressure homogenization technique followed by lyophilization with trehalose as cryoprotectant.Diabetes was induced into rats by the administration of fructose (10%) in drinking water for six weeks.After induction of diabetes, rats were divided into four groups for the oral ingestion of NI, NI-SLN and/or vehicles and their effects on blood glucose levels, oral glucose tolerance test (OGTT), lipid profile, biochemical parameters, electrolytes and histopathology were observed.Single dose administration and treatment with NI-SLN showed significant glucose lowering efficacy in fructose-induced diabetic rats.Although NI and NI-SLN did not alter the fasting blood glucose level in normal rats, diabetic rats treated with NI-SLN resulted in significant reduction in glucose level for 24 hr.In OGTT, NI-SLN exhibited significant antihyperglycemic activity in both normal and diabetic rats.So, NI-SLN has better glucose lowering efficacy than that of pure NI in diabetic rats.The survival rates in rats among the treatment groups were 100%.Treatment with