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Pharmacology & Pharmacy 2023年第5期14卷 156-175页

作者： Mst. Boby Aktar Bithy Milon kumar Ghosh Ashim kumar Md. Rafiqul Islam Khan Mir Imam Ibne Wahed ranjan kumar barman Laboratory of Pharmaceutics Department of Pharmacy Faculty of Science University of Rajshahi Rajshahi Bangladesh Department of Pharmacy Faculty of Biological Sciences Islamic University Kushtia Bangladesh

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.

关键词： Carplex-67 Cefuroxime Axetil Improved Dissolution PEG-4000 Solid Dispersion Solvent Evaporation

Development and Evaluation of Stable Paracetamol Loaded Solid Dispersion with Enhanced Analgesic and Hepatoprotective Property

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Pharmacology & Pharmacy 2023年第4期14卷 123-143页

作者： Ashim kumar Milon kumar Ghosh Mst. Boby Aktar Bithy Md. Rafiqul Islam Khan Md. Monimul Huq Mir Imam Ibne Wahed ranjan kumar barman Laboratory of Pharmaceutics Department of Pharmacy Faculty of Science University of Rajshahi Rajshahi Bangladesh Department of Pharmacy Faculty of Biological Sciences Islamic University Kushtia Bangladesh Department of Statistics Faculty of Science University of Rajshahi Rajshahi Bangladesh

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.

关键词： Paracetamol Solid Dispersion Dissolution Analgesic Activity Hepatocyte Particle Surface Property Stability

Formulation and Characterization of Fenofibrate Loaded Solid Dispersion with Enhanced Dissolution Profile

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Pharmacology & Pharmacy 2019年第7期10卷 343-355页

作者： Milon kumar Ghosh Mir Imam Ibne Wahed Md. Ashraf Ali ranjan kumar barman Department of Pharmacy Faculty of Science University of Rajshahi Rajshahi Bangladesh Department of Pharmacy Faculty of Biological Sciences Islamic University Kushtia Bangladesh Department of Pharmacy Mawlana Bhashani Science and Technology University Tangail Bangladesh

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.

关键词： Fenofibrate Solid Dispersion Dissolution Solvent Evaporation Carplex-80 PEG-4000

Improving Flow Property of Nifedipine Loaded Solid-Lipid Nanoparticles by Means of Silica for Oral Solid Dosage Form

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Pharmacology & Pharmacy 2014年第12期5卷 1119-1129页

作者： ranjan kumar barman Yasunori Iwao Shuji Noguchi Mir Imam Ibne Wahed Shigeru Itai Department of Pharmaceutical Engineering and Drug Delivery Science School of Pharmaceutical Sciences University of Shizuoka Shizuoka Japan Department of Pharmacy Faculty of Science University of Rajshahi Rajshahi Bangladesh

In this study, a new formulation of silica nanocomposite containing nifedipine (NI) loaded freeze-dried solid-lipid nanoparticles (NI-SLNs) and silica have been developed with improved flowability of powders, which can lead to the formulation of a widely acceptable oral dosage form. The stable NI-SLNs were prepared using two phospholipids, hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol mixed with 2.5% w/v trehalose as a cryoprotectant followed by lyophilization. We employed various grades of two types of silica, such as fumed and precipitated. Silica improved the poor flow property of NI-SLNs to good category as per USP-29. In addition, most of the silica nanocomposites showed the satisfactory results in their physicochemical properties such as particle size, polydispersity index, zeta potential, and recovered potency by around 100 nm, 0.3, -50 mV, and 80%, respectively. Furthermore, it was found that NI-SLNs were easily released form nanocomposites within 30 min, therefore, suggesting an improvement of drug dissolutions. Among them, precipitated silica cooperated fairly in improving the powder characteristics as well as the physicochemical, morphological, and pharmaceutical properties.

关键词： Silica Solid-Lipid Nanoparticle Solid Dosage Form Nifedipine Flowability

<i>In Vivo</i>Pharmacokinetic and Hemocompatible Evaluation of Lyophilization Induced Nifedipine Solid-Lipid Nanoparticle

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Pharmacology & Pharmacy 2014年第5期5卷 455-461页

作者： ranjan kumar barman Yasunori Iwao Md. Rafiqul Islam Yuka Funakoshi Shuji Noguchi Mir Imam Ibne Wahed Shigeru Itai Department of Pharmaceutical Engineering and Drug Delivery Science Graduate School of Pharmaceutical Sciences University of Shizuoka Shizuoka Japan Department of Pharmacy Faculty of Biological Science and Technology Jessore University of Science and Technology Jessore Bangladesh Department of Pharmacy Faculty of Science University of Rajshahi Rajshahi Bangladesh

Nifedipine-solid-lipid nanoparticles lyophilized with trehalose (NI-SLN-Tre) were prepared by the high pressure homogenization of a roll mixture consisting of NI and hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol, and in vivo pharmacokinetic properties and their hemocompatibility were determined and compared with those of a NI-SLN suspension. The resulting pharmacokinetic data demonstrated that although no significant differences were observed between the time of peak concentration (Tmax), peak plasma concentration (Cmax), and the area under the curve (AUC0→∞) values of both administrated samples, NI tended to be absorbed to a much greater extent from the lyophilized NI-SLN-Tre suspensions because of the enhanced solvation of NI-SLN in gastrointestinal fluid, derived from formation of hydrogen bonds between the polar head groups of the lipids and the O-H groups of trehalose. Furthermore, the results of a hemolysis assay revealed that the NI-SLN and NI-SLN-Tre suspensions showed good hemocompatibility properties with hemolysis values of less than 5%. Taken together, the results of this study demonstrate that NI-SLN-Tre exhibits suitable pharmacokinetic properties and good biocompatibility.

关键词： Nifedipine Solid-Lipid Nanoparticles Lyophilization Pharmacokinetics Hemocompatibility

Preparation and Antidiabetic Effect of Orally Administered Nifedipine‐Loaded Solid Lipid Nanoparticles in Fructose-Induced Diabetic Rats

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Pharmacology & Pharmacy 2018年第10期9卷 457-471页

作者： Sabarni Sarker Md. Ashraf Ali ranjan kumar barman Shuji Noguchi Yasunori Iwao Shigeru Itai Mir Imam Ibne Wahed Department of Pharmacy Faculty of Life and Earth Sciences Jagannath University Dhaka Bangladesh Department of Pharmacy Mawlana Bhasani University of Science of Technology Tangail Bangladesh Department of Pharmacy Faculty of Science University of Rajshahi Rajshahi Bangladesh Laboratory of Pharmaceutics Faculty of Pharmaceutical Sciences Toho University Tokyo Japan Department of Pharmaceutical Engineering and Drug Delivery Science School of Pharmaceutical Sciences University of Shizuoka Shizuoka Japan

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 NI-SLN significantly improved lipid profiles than NI alone and the effect was dose-dependent. Administration of NI-SLN significantly reduced uric acid, creatinine levels and maintained a good cationic balance. After two weeks of NI-SLN treatment, hepatocytes regained their normal architecture, and the beneficial effect could be correlated with the reduction of SGOT and total bilirubin levels. Therefore, NI-SLN was found to be useful for the enhancement of bioavailability and exhibit

关键词： Formulation Solid Lipid Nanoparticle Calcium Channel Blocker Nifedipine Fructose Diabetes

Accelerated Aqueous Solubility and Antibacterial Activity of Cefuroxime Axetil Using Microcrystalline Cellulose as Carrier

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Pharmacology & Pharmacy 2020年第8期11卷 159-173页

作者： Moushumi Tabassoom Salam Ashim kumar Akito Hata Hiromu Kondo Md. Abdus Salam Mir Imam Ibne Wahed Md. Rafiqul Islam Khan ranjan kumar barman Laboratory of Pharmaceutics Department of Pharmacy Faculty of Science University of Rajshahi Rajshahi Bangladesh Laboratory of Pharmaceutical Engineering & Drug Delivery Science School of Pharmaceutical Science University of Shizuoka Shizuoka Japan Department of Basic Medical Sciences Faculty of Medicine International Islamic University Malaysia Kuantan Malaysia

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

关键词： Cefuroxime Axetil Dispersion Solubility Antibacterial Activity

Improvement of Dissolution Rate of Gliclazide Using Solid Dispersions with Aerosil 380 and Its Effect on Alloxan Induced Diabetic Rats

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Pharmacology & Pharmacy 2019年第8期10卷 365-385页

作者： Subrata Paul Md. Nur Islam Md. Ashraf Ali ranjan kumar barman Mir Imam Ibne Wahed Bytul M. Rahman Department of Pharmacy Faculty of Science Rajshahi University Rajshahi Bangladesh Department of Pharmacy Faculty of Life Science Mawlana Bhashani Science and Technology University Tangail Bangladesh

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.

关键词： In-Vitro Dissolution Fumed Silica Solid Dispersions Gliclazide Alloxan Diabetes

Formulation Development and <i>In-Vivo</i>Evaluation of Atorvastatin Calcium Solid Dispersion in Streptozotocin Induced Diabetic Mice

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Pharmacology & Pharmacy 2018年第9期9卷 395-414页

作者： Md. Shahin Sarker ranjan kumar barman Md. Ashraf Ali Shuji Noguchi Yasunori Iwao Shigeru Itai Mir Imam Ibne Wahed Department of Pharmacy Faculty of Science University of Rajshahi Rajshahi Bangladesh Department of Pharmacy Mawlana Bhasani University of Science of Technology Tangail Bangladesh Laboratory of Pharmaceutics Faculty of Pharmaceutical Sciences Toho University Chiba Japan Department of Pharmaceutical Engineering and Drug Delivery Science School of Pharmaceutical Sciences University of Shizuoka Shizuoka Japan

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 co

关键词： Solid Dispersion Atorvastatin Poor Aqueous Solubiity Streptozotocin Diabetic Mice

Clinical outcome of orbital apex syndrome in COVID associated mucormycosis patients in a tertiary care hospital

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International Journal of Ophthalmology(English edition) 2022年第4期15卷 527-532页

作者： Smiti Rani Srivastava Purban Ganguly Debasis barman Sudip Das Manimoy Bandyopadhyay Asim kumar Ghosh Subhra Sarkar Amitabha Sengupta Sarbari Swaika Pritam Chatterjee Amit kumar Gupta Alok ranjan Mondal Soumyajit Guha Sinjita Dutta Souvik Adhikari Aditi Kaushik Partha Sundar Biswas Asif Ayub Department of Ophthalmology Institute of Post Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial HospitalKolkata 999008India

AIM: To share clinical pattern of presentation, the modalities of surgical intervention and the one month postsurgical outcome of rhino-orbito-mucormycosis(ROCM) ***: All COVID associated mucormycosis(CAM) patients underwent comprehensive multidisciplinar y examination by ophthalmologist, otorhinolaryngologist and physician. Patients with clinical and radiological evidence of orbital apex involvement were included in the study. Appropriate medical and surgical intervention were done to each patient. Patients were followed up one-month post intervention. RESULTS: Out of 89 CAM patients, 31(34.8%) had orbital apex syndrome. Sixty-six(74.2%) of such patients had pre-existing diabetes mellitus, 18(58%) patients had prior documented use of steroid use, and 55(61.8%) had no light perception(LP) presenting vision. Blepharoptosis, proptosis, complete ophthalmoplegia were common clinical findings. Seventeen(19.1%) of such patients had variable amount of cavernous sinus involvement. Endoscopic debridement of paranasal sinuses and orbit with or without eyelid sparing limited orbital exenteration was done in most cases, 34(38.2%) patients could retain vision in the affected eye. CONCLUSION: Orbital apex involvement in CAM patients occur very fast. It not only leads to loss of vision but also sacrifice of the eyeball, orbital contents and eyelids. Early diagnosis and prompt intervention can preserve life, vision and spare mutilating surgeries.

关键词： rhino-orbito-cerebral mucormycosis COVID associated mucormycosis orbital exenteration endoscopic paranasal sinus debridement orbital apex syndrome