• Bulletin of the Korean Chemical Society
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• v.32 no.5
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• pp.1587-1592
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• 2011

The aim of the present study was to improve the solubility and bioavailability of a poorly water-soluble drug in human body, using a solid dispersion technique (hot melt extrusion). The solid dispersion was prepared by cooling the hot melt of the drug in the carrier (Vitamin E TPGS and PVP). The dissolution rate of formulation 1 from a novel formulation prepared by solid dispersion technique was equal to release of formulation 6 (40% of eprosartan mesylate is in contrast to teveten$^{(R)}$) within 60 min (Table 1). The oral bioavailability of new eprosartan mesylate tablet having vitamin E TPGS and PVP K29 was tested on rats and dogs. Of the absorption enhancer and polymer tested, vitamin E TPGS and PVP K29, resulted in the greatest increases of AUC in animals (about 2.5-fold increase in rat and dog). When eprosartan mesylate was mixed with the absorption enhancer and polymer in a ratio of 2.94:2:1, vitamin E TPGS and PVP K29 improved eprosartan mesylate bioavailability significantly compared with the conventional immediate release (IR) tablet Teveten$^{(R)}$ (formulation 7). These results show that solid dispersion using vitamin E TPGS and PVP K29 is a promising approach for developing eprosartan mesylate drug products.

• The Journal of Korean Medicine
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• v.35 no.2
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• pp.47-59
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• 2014

Objectives: Most drug interactions are attributed to the inhibition or induction of the activity of cytochrome P450s (CYP450). Although the regulation of CYP450s by drugs has been widely reported, there have been few studies on influence of traditional herbal formulas on the drug-metabolizing enzymes. Because herbal formulas have been used traditionally to treat various diseases and because herb-drug interactions are crucial factors determining therapeutic efficacies, a systematic evaluation of the effects of herbal formulas is important. Methods: The effects of Galgeun-tang (GGT, gegen tang), Gumiganghwal-tang (GMGHT, jiuweiqianghuo tang), Insampaedok-san (ISPDS, renshenbaidu powder), Samsoeum (SSE, shensu drink), Socheongryong-tang (SCRT, xiaoqinglong-tang) and Sosiho-tang (SSHT, xiaochaihu tang) that are traditional herbal formulas used to treat common cold, on drug-metabolizing enzymes were evaluated through an in vitro CYP3A4, CYP2D6, CYP2C19 and CYP2E1 inhibition assay to assess its interaction potential with synthetic drugs. The inhibitory effects of herbal formulas were characterized with $IC_{50}$ values. Results: These six herbal formulas inhibited the activities of CYP3A4, 2C19, 2D6 and 2E1, in a concentration-dependent manner. Among the six herbal formulas, GGT critically inhibited CYP2C19, CYP2D6 and CYP2E1. GMGHT also inhibited CYP2D6 and CYP2E1 to a greater extent than the other CYP450 isozymes. Additionally, SSE and SSHT may change the effects of medicines that depend primarily on the CYP2C19 and CYP2E1 pathways. On the other hand, ISPDS and SCRT were not inhibited CYP3A4, CYP2C19, CYP2D6 and CYP2E1-mediated metabolism. Conclusions: These findings provide useful information regarding the safety and effectiveness of herbal formulas.

• Journal of Pharmaceutical Investigation
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• v.41 no.4
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• pp.217-225
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• 2011

The aim of this work was to prepare porous osmotic pump tablets for controlled delivery of Aceclofenac. Aceclofenac solid dispersion was prepared to improve the solubility by using the drug - carrier (Mannitol) ratio of 1:1. The osmotic pump tablets were prepared using the solid dispersed product of Aceclofenac. The formulation contains potassium chloride as osmotic agent, cellulose acetate as semipermeable membrane, poly ethylene glycol (PEG 4000) as pore former and sodium lauryl sulphate (SLS) as solubility enhancer. The formulations were designed by the general factors such as osmotic agent and pore former. All formulations were evaluated for various physical parameters and, the in vitro release studies were conducted as per USP. The drug release kinetic studies such as zero order, first order, and Higuchi and Korsmeyer peppas were determined and compared. All the formulations gave more controlled release compared to the marketed tablet studied. Numerical optimization techniques were applied to found out the best formulation by considering the parameter of in vitro drug release kinetics and dissolution profile standards. It was concluded that the porous osmotic pump tablets (F7) composed of Aceclofenac solid dispersion/Potassium chloride/Lactose/Sodium lauryl sulphate/Magnesium Stearate (400/40/95/10/5, mg/tab) and coating composition with Cellulose acetate/ PEG 4000 (60/40 %w/w) is the most satisfactory formulation. The porous osmotic pump tablets provide prolonged, controlled, and gastrointestinal environment-independent drug release.

• Journal of Pharmaceutical Investigation
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• v.32 no.4
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• pp.299-303
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• 2002

The oral bioavailability of itraconazole is variable and low in fasting state. This is mainly due to the low solubility of this drug. Bioavailability can be improved by changing the formulation and it is general that the liquid preparations show greater bioavailability than the solid dosage forms such as tablets and capsules do. Benzyl alcohol-water binary mixture showed the excellent solubilizing capacity for itraconazole but the release of the drug from the preparation needs to be enhanced. In this study, various nonionic surfactants and hydrophilic polymers, poloxamers, were screened to investigate their effects on the releasε of itraconazole from the liquid preparations. Poloxamer 407 showed the most enhancing effect on the drug release and the release rate was proportional to thε amount of poloxamer 407 added. A liquid preparation of itraconazole, consisting of benzyl alcohol/water/poloxamer 407 ternary solvent system, releasεd more than 80% of the total drug amount at 5 min and showεd the possibility of a new formulation development.

• CELLMED
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• v.10 no.2
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• pp.16.1-16.8
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• 2020

Standardization of drug deals with confirmation of drug identity and determination of drug quality and purity. Unani herbal formulations are used in traditional medicine for the treatment of various diseases. Cancer is a disease which causes abnormal, uncontrolled growth of body tissue or cells, which tend to proliferate in an uncontrolled way. Spread of cancer from site of origin to other organs of the body is called metastasis. It is a hyper proliferative disorder involving, transformation, dysregulation of apoptosis, invasion and angiogenesis. The present study aimed to standardize a classical Unani formulation (CUF) described as anticancer properties. The CUF has been used for anti-cancerous activity (Dāfi'-i-saraṭān) in human population by Unani physicians for centuries. The standardization parameters carried out for classical Unani formulation are pharmacognostical studies, physicochemical parameters, high-performance thin layer chromatography (HPTLC), microbial load, aflatoxins, and heavy metals revealing specific identities and to evaluate Pharmacopoeial standards. Experiment and the data obtained established the Pharmacopoeial standards for this formulation for identification and quality control purpose. The CUF has been successfully standardized and standard operating procedures (SOPs) for its preparation has been laid down which may serve as a standard reference in future. The standardization data of this formulation may be used as a standard guideline for preparation of the formulation in future.

• Journal of Pharmaceutical Investigation
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• v.22 no.3
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• pp.17-34
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• 1992

A novel drug delivery system, detergent-phospholipid mixed micelles as proliposomes, for water-insoluble compounds was developed by investigating (i) spontaneous formation of small unilamellar vesicles (SUV) from bile salt-egg phosphatidylcholine mixed micelles, (ii) the molecular mechanism of micelle-to-vesicle transition in aqueous mixtures of detergent-phospholipid, (iii) preparation and screening of a suitable liposomal formulation for a lipophilic drug: solubilization of the drug within the lipid bilayer, evaluation of the solubility limit, and characterization of the resulting product with respect to the physical properties and stability of the drug in the system, and (iv) testing antitumor activity in vitro. The results showed that the new carrier had a strong possibility to be a biocompatible universal formulation for water-insoluble drugs.

• Journal of Pharmaceutical Investigation
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• v.40 no.1
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• pp.33-38
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• 2010

Sibutramine is a serotonin-norepinephrine reuptake inhibitor indicated for the management of obesity in conjunction with a reduced calorie diet. The oral administration of sibutramine is followed by its dose-related side effects. In this study, sibutramine was formulated into drug in adhesive (DIA) patches in an attempt to overcome these problems. The effects of different formulation variables including pressure-sensitive adhesive (PSA), loading amount of drug, thickness of matrix and enhancer on the skin permeation of the drug were evaluated using excised hairless mouse skin. In the acrylic adhesive with carboxyl functional group, low release of sibutramine was observed due to the strong interaction between carboxyl group of adhesive and amine group of sibutramine. The acrylic adhesive without functional group provided good adhesion force and allowed high drug loading. Changing drug load as well as thickness of the matrix was found to alter permeation rate. $Crovol^{(R)}$ PK40 and $Crovol^{(R)}$ A40, were found to be effective enhancers for sibutramine. The optimized patch contained 20% sibutramine, and 5% $Crovol^{(R)}$ A40 as permeation enhancer, in $80\;{\mu}m$ thick Duro-$Tak^{(R)}$ 87-9301 matrix.

• Journal of Pharmaceutical Investigation
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• v.39 no.6
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• pp.437-443
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• 2009

To develop a topical bioadhesive formulation of clotrimazole for enhanced transdermal delivery, hydroxypropyl methylcellulose gel containing permeation enhancer was formulated and permeation studies were carried out. The release characteristics of the drug from the gel formulation were examined according to the receptor medium, drug concentration, and temperature. The rate of drug release from the gel increased with increasing drug concentration and temperature. The activation energy (Ea) of drug permeation, which was calculated from the slope of log P versus 1/T plots, was 14.41kcal/mol for a 1%(w/w) loading dose. The enhancer, such as saturated, unsaturated fatty acids, pyrrolidones, propylene glycol derivatives, glycerides, and non-ionic surfactants, were incorporated onto the gels to increase the amount of drug permeation into the skin. Among the enhancers used, polyoxyethylene 2-oleyl ether showed the highest level of enhancement. These results show that clotrimazole gels containing polyoxyethylene 2-oleyl ether could be used for the enhanced transdermal delivery of clotrimazole.

• Journal of Microbiology and Biotechnology
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• v.9 no.1
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• pp.50-55
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• 1999

To develop a new form of controlled release dosage for administering for indomethacin (IND), two formulations of IND-loaded nanoparticles were designed based on polysaccharide (guar) derivatives. Nanoparticles prepared by the dialysis method were characterized with respect to morphology, size distribution, drug content, and in vitro drug release. Morphological studies by scanning electron microscopy (SEM) indicated that guar acetate (GA) nanoparticles were spherical in shape and had a smooth surface. The particle size distributions of formulation I (40mg of GA) and formulation II (80mg of GA) were shown to be $250.78\pm185.13nm$ and $718\pm145.90nm$ in distilled water ($20$^{\circ}C$), respectively. The drug loading efficiencies of nanoparticles were approximately 26% and 31% for formulations I and II, respectively. The differential scanning calorimetry (DSC) results indicated that the IND was perfectly distributed within GA nanoparticles. We also found, from the X-ray diffractometry analysis, that a decrease in the degree of crystallinity of the drug occurred in the nanoparticles. No changes between the original IND and the released IND from GA nanoparticles were detected by FT-IR. Using guar acetate, it is possible to design nanoparticles which allow the controlled release of IND over an extended period of time.

• CELLMED
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• v.11 no.1
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• pp.2.1-2.8
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• 2021

The clinical condition Amnesia causes difficulty in learning new information and the inability to recall past events. It is primarily concerned with recent memory loss. Majoon-e-Nisyan (MJN) is a polyherbal Unani formulation, present in a semi-solid form. It is widely used potent drug of the Unani System of Medicine (USM) for treating Nisyan (amnesia). In the present study polyherbal Unani formulation, MJN has been studied for its quality control and acute toxicity. Standardization (quality control) of drugs deals with drug identity, drug quality and purity determination. Standardization of MJN had been done as per the Unani pharmacopoeial parameters approved by World Health Organization (WHO) - Pharmacognostical parameters, Physico-chemical parameters, high-performance thin-layer chromatography (HPTLC), microbial load, aflatoxin, and heavy metals. Solvents and chemicals used in the study were of analytical grade and used instrument were calibrated. By conducting an acute oral toxicity study in rats, the safety of MJN was assessed. The limit test method of OECD guideline 425 was followed in the study. Results of standardization and standard operating procedures (SOPs) for preparation of MJN may serve as the standard reference in the future. The data generated in the study for the quality control of MJN proved the quality of formulation and shows that MJN is not toxic in rats following acute dosing up to 2000 mg/kg bw. The data obtained in the paper for MJN may be used as a standard guideline for preparation of the formulation which can save time, cost, and resources for future research endeavours.