Metformin HCl Oral Preparation Exhibits Anticancer Activity In-vitro in a Human Non-small Cell Lung Tumour Cell Line

@#Introduction: The most common variety of lung cancer is non–small cell lung cancer (NSCLC) accounting for 84% of new cases. Surgery, chemotherapy and radiation are the primary treatment option. Metformin has recently been demonstrated to have an anti-tumour impact on various cancer cells. The goal of this investigation was to determine the growth inhibitory, antiproliferative, cytotoxic, apoptotic and cell cycle arrest properties of metformin HCl oral tablets on the A549 lung carcinoma cell line. Methods: The cells were treated with different dosages of an oral preparation of metformin, with untreated cells used as a control. The Trypan Blue Exclusion Assay was used to determine metformin’s inhibitory and cytotoxic effects. Flow cytometry was used to evaluate apoptosis and cell cycle arrest. Results: In a dose-dependent manner, metformin HCl was able to reduce the viability of treated cells compared to the untreated control. Cell proliferation was considerably inhibited in the treated group with the IC50 dose than in the untreated control group and the IC50 dose showed no cytotoxic effect on L929 cells. Induction of apoptosis and cell cycle arrest was observed in the IC50 dose-treated group by Flow cytometry analysis and data showed metformin oral drug causes early apoptosis and a considerable cell increase in the S phase of the cell cycle. Conclusion: Metformin inhibits cell growth and induces apoptosis and cell cycle arrest in the cell line. A comprehensive proteome examination is required to understand more about the mechanism of action of the oral metformin HCl on cancer cells

Development of metformin HCl granules using brown flaxseed mucilage as a retardant polymer: effects of polymer and drug ratio

Abstract Flaxseed (Linum usitatissimum L.) is the seed of a multipurpose plant of pharmaceutical interest, as its mucilage can be used as a natural matrix to develop extended-release dosage forms and potentially replace synthetic polymers. In this study, a 3² factorial design with two replicates of the central point was applied to optimize the development of extended-release granules of metformin HCl. The total fiber content of the mucilage as well as the friability and dissolution of the formulations were evaluated. The lyophilized mucilage presented a high total fiber content (42.63%), which suggests a high efficiency extraction process. Higher concentrations of the mucilage and metformin HCl yielded less friable granules. In addition, lower concentrations of metformin HCl and higher concentrations of the mucilage resulted in slower drug release during the dissolution assays. The release kinetics for most formulations were better represented by the Hixson-Crowell model, while formulations containing a higher concentration of the mucilage were represented by the Korsmeyer-Peppas model. Nonetheless, five formulations showed a longer release than the reference HPMC formulation. More desirable results were obtained with a higher concentration of the mucilage (13-18%) and a lower concentration of metformin (40%).

Investigation on formulation parameters of donepezil HCl loaded solid lipid nanoparticles

Abstract Donepezil-HCl is a member of the acetylcholinesterase inhibitors that is indicated for the symptomatic treatment of Alzheimer's disease (AD) and has many side effects. In this study, to reduce the side effects of Donepezil-HCl and increase the penetration of the drug through the blood-brain barrier, we aimed to design a solid lipid nanoparticle (SLN) formulation. The effects of the different formulation parameters, such as homogenization speed, sonication time, lipid and drug concentration, surfactant type and concentration, and volume of the aqueous phase, were assessed for optimization. The particle size and PDI increased with increasing lipid concentration but decreased with increasing amounts of surfactant (Tween 80) and co-surfactant (lecithin). When the homogenization rate and sonication time increased, the particle size decreased and the encapsulation efficiency increased. The optimized formulation exhibited particle size, PDI, encapsulation efficiency, and zeta potential of 87.2±0.11 nm; 0.22±0.02; 93.84±0.01 %; -17.0±0.12 mV respectively. The in vitro release investigation revealed that approximately 70% of Donepezil-HCl was cumulatively released after 24 hours. TEM analysis proved that spherical and smooth particles were obtained and formulations had no toxic effect on cells. The final optimized formulation could be a candidate for Donepezil-HCl application in Alzheimer's treatment with reduced side effects and doses for patients

Carboxymethylation Of Karaya Gum: Application In Gastroretentive Drug Delivery For Sustained Release Of Model Drug

Karaya gum (KG) is one of the least soluble of the gums. It does not dissolve in water to give a clear solution but instead absorbs water rapidly to form viscous colloidal sols. Carboxymethylation of Karaya gum is expected to improve its aqueous solubility and gelling behavior. Another objective of the research is to evaluate the potential of carboxymethylated Karaya gum (CMKG) as drug release modulator (in acidic dissolution medium) when combined with HPMC K15M based polymeric matrices bearing Propranolol HCl. In the present study, KG was carboxymethylated using Williamson Ether synthesis. FTIR spectroscopy confirmed the formation of CMKG. The prepared CMKG was used in conjunction with HPMC K15M as a polymer matrix in the formulation capsule dosage form, using Propranolol HCl as model drug. The filled capsules were then coated with Gelucire 43/01 to convert them into hydrodynamically balanced (HBS) capsule dosage form. Dextrose & fructose were also added to the drug-polymer mix as osmogen to facilitate the drug release. The degree of substitution of CMKG was found to be 0.87. HBS capsule dosage forms remained buoyant on 0.1 HCl for up to 6 hr, the buoyancy was attributed to the Gelucire 43/01 coating around the capsule shell. From the experimentation it was observed that CMKG, when mixed with HPMC K15M at 1:3 ratios, extended the release of model drug from HBS capsule dosage forms in 0.1 HCl. At CMKG: HPMC K15M ratio 2:1, release of Propranolol Hydrochloride from hydrodynamically balanced (HBS) capsules revealed fast drug release in 0.1 HCl. From the observations it is evident that KG is amenable to carboxymethylation to form CMKG. It is also evident that it is advantageous to combine CMKG with HPMC K15M as release modulator to retard the release of Propranolol HCl in acidic dissolution medium.

Venlafaxine Hydrochloride Controlled Release Bilayer Tablets: Optimization Of Formulation Variable By Using Dyspnea On Exertion

The current research work was to develop bilayer tablet of venlafaxine hydrochloride to increase drug efficacy for efficient treatment of depression. The satisfactory result of treatment can be achieved upon the maintenance of drug concentration within an effective level in the body, so a uniform and constant drug supply are desirable. An immediate layer of venlafaxine HCl was formulated using super disintegrants, i.e., croscarmellose sodium (CCS) and sodium starch glycolate (SSG); tablet compact by direct compression. HPMC K100M and ethylcellulose (EC) were utilized as release retarding polymers in sustained release layer by wet granulation technique with the help of PVP K30 in IPA solution (10%) as a granulating agent. Full 32 factorial designs were used to find out the optimum quantity of release retardant polymers. Bilayer tablet was evaluated for various parameters, i.e. hardness, friability, weight variation, % drug content, disintegration time (IR layer), and % drug release study. Statically, an analysis was carried out using factor X1 (HPMC K100M) and X2 (EC) for dependent variable % drug release at 8, 12, and 20 hours. A formulation was optimized and a formulation containing 305.36 mg of HPMC K100M and 54.03 mg of ethyl cellulose. Optimized formulation show 47.12 ± 2.1, 59.89 ± 2.2, and 89.06 ± 2.3 drug release at 8, 12, and 20 hours, respectively, which is almost similar to theoretical dose calculation with similarity factor f2 97, 99, and 98%, respectively. Bilayer tablet formulation was observed to be stable and fulfilled all compendia specifications.

Single-run reversed-phase HPLC method for determining sertraline content, enantiomeric purity, and related substances in drug substance and finished product / 药物分析学报

A direct enantio-, diastereo-, and chemo-selective high-performance liquid chromatographic method was developed for determining the content, enantiomeric purity, and related substances of the chiral antidepressant drug sertraline HCl in a single chromatographic run. The separation was achieved on a chiral stationary phase based on amylose tris(3-chloro-5-methylphenylcarbamate) under reversed-phase conditions. The method was optimized by evaluating the influence of the temperature and mobile phase composition on the retention and selectivity. The application of the single-run approach allowed to baseline resolve all investigated species in less than 15 min, without using buffers or tandem-coupled columns. The chromatographic method was validated according to the guidelines of the Official Medi-cines Control Laboratory and applied to control the content of sertraline HCl and related chiral sub-stances in a generic antidepressant formulation.

Formulation And Optimization Of Terbinafine Hcl Solid Lipid Nanoparticles For Topical Antifungal Activity

Objective: Solid lipid nanoparticles (SLNs) are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery and research. The aim of this study was to develop and characterize SLNs formulae of Terbinafine HCl (TFH) for topical drug delivery applications. Methods: SLNs were prepared using the solvent injection technique. Glyceryl Monostearate (GMS) served as the lipid base. Three stabilizers; Tween 80, Cremophor RH40, and Poloxamer 188, were used. The effect of stabilizer type and concentration, as well as the lipid concentration, were studied, factorial design of 32*21was applied. The prepared SLNs were characterized regarding their particle size, zeta potential, polydispersity index (PDI), entrapment efficiency percent (EE %), and physicochemical stability. The selected formulae were subjected to further investigations such as morphological studies, in vitro release studies, and Infrared (IR) spectroscopy. They were compared with the marketed cream Lamifen® in term of their antifungal activity against Candida albicans. Results: Lipid concentration, together with the type and concentration of stabilizer, appeared to be the main cornerstones which affect the formation of SLNs. Smaller particle size was observed when increasing the stabilizer concentration and decreasing the lipid concentration. Higher EE% was observed when increasing both the stabilizer and the lipid concentrations. Formulae (F6, F12 andF19) were selected as the most suitable SLNs with optimum particle size of 480.2±18.89, 458.6±12.45 and 246.7±10.5 nm, respectively as well as the highest EE% of 87.13±0.19, 93.69±0.7 and 95.06±0.25, respectively. In vitro microbiological screening of their antifungal activity showed significantly larger zones of inhibition of diameters 25.9±0.25, 25±0.35 and 24.67±0.36 mm, respectively in comparison with the marketed Lamifen® cream which showed a zone of 11.2±0.44 mm diameter. Conclusion: Applying SLNs containing TFH as topical antifungal preparations may be considered as a very promising option as they show good physicochemical characterization with high antifungal activity, which delineates them as a promising dosage form for topical antifungal treatment.

An Evaluation of the Efficacy of Ketamine Gargle and Benzydamine Hydrochloride Gargle for Attenuating Post Operative Sore Throat: A Prospective Randomized, Placebo Controlled Single- Blind Study

Post-operative sorethroat (POST) is a well-recognized complication in patients with endotracheal intubation for general anaesthesia. Many pharmacological measures for attenuating POST are being used during anaesthesia. In our study we compared the effectiveness of ketamine and benzydamine hydrochloride versus a placebo as preoperative gargle in decresing the incidence and severity of POST in patients undergoing endotracheal intubation for general anaesthesia. Methods: A total of 90 patients aged between 18-60 years of ASA I-II of either sex were randomly assigned into three groups of 30 patients each . Group 1(C) received distilled water,group2(BH) received 15 ml of benzydamine hcl(0.15%) and group 3(K) received preservative free ketamine 40 mg as preoperative gargle 10 min before induction. The incid- ence of POST was recorded at 2,4 and 24 hr post operatively. Results: The three groups were comparable in term of demographic characteristics. The incidence and severity of POST is much more in group 1(C) i.e control group (30%) after 24 hr compared to group 2 (BH) 0% and group 3(K)3.5%. There was no significant difference of POST in group 2(BH) and group 3(K). Conclusion: From our study it can be concluded that both benzydamine and ketamine gargle significantly reduces the incidence and severity of POST compared to ditilled water gargle up to 24 hr in the patients undergoing general anaesthesia with endotracheal intubation. Both the Benzydamine and ketamine gargles are safe, simple and equally effective in reducing POST.

A validated LC-ESI-MS/MS method for the quantification of Selegiline HCl in bulk and pharmaceutical formulation

Selegiline HCl is an irreversible MAO-B inhibitor used to reduce symptoms in early-stage Parkinson’s disease. It isused as an adjunct to drugs, such as L Dopamine (L-DOPA). The present study is designed to develop and validatea rapid, sensitive, and straightforward separation method with Electrospray ionization and triple quadrupole massanalyzer for the quantification of Selegiline HCl in bulk and pharmaceutical formulation. Zorbax C18 column (50 mm× 4.6 mm i.d, 5 µ particle size) was used for the separation of analyte and internal standard. The samples were elutedusing 0.1% Formic acid in water and Methanol (40:60%v/v) which is delivered at 0.5 ml/minute flow rate, with achromatographic runtime of 5 minutes. The eluents were monitored using a tandem mass spectrometer equipped withan electrospray ionization in positive mode and a triple quadrupole mass analyzer. The detection was carried out inmultiple reaction-monitoring mode by quantifying the m/z 188.05→91.10 ion transition pair; with collision energy−29.0 V for Selegiline HCl. Linearity was achieved over the concentration range 3.5–6.5 ng/ml for the developedmethod. The limit of detection and limit of quantification were found to be 0.2 and 0.5 ng/ml, respectively. Thecorrelation coefficient (r2) value was ≥0.9985 for Selegiline HCl. This method offers a sensitive quantification ofSelegiline HCl in the pharmaceutical formulation.

Formulation And Characterization Of Ondansetron Hydrochloride Matrix Tablets For Sustained Drug Delivery

The objective of proposed work was to develop Ondansetron Hydrochloride (OND HCl) sustained release matrix tablets for the better treatment of vomiting for extended period of time. Sustained release matrix tablet is the drug delivery system that is designed to achieve a prolonged therapeutic effect by continuously releasing medication over an extended period of time after administration of single dose. The matrix tablets of OND HCl were prepared by direct compression method using varying ratio of hydroxy propyl methyl cellulose (HPMC) and ethyl cellulose. The bends of tablets were evaluated for bulk and tapped density, % compressibility index and angle of repose and powder of all formulations blend exhibited that low interparticle friction and excellent flow characteristics. The prepared matrix tablets were then assessed for different physical tests like consistency of weight, thickness, hardness, friability, drug content and in vitro drug release. Each batch of the OND HCl matrix tablets were of good quality as to hardness, thickness, friability and % medicament content. The in vitro drug release study was done for 2 hours by utilizing paddle technique in 0.1N HCl (pH 1.2) as dissolution media and 6 hours using phosphate buffer (pH 6.8) as dissolution media. The drug release study showed that all formulation FMT-1, FMT-2, FMT-3, FMT-4, FMT-5 and FMT-6 were provide the drug release on sustained manner up to 8 hrs. Amongst the developed matrix tablets formulations, FMT-2 containing ethyl cellulose (100 mg) was optimized as best because FMT-2 show highest drug release profile and promoting the sustained release of drug, which could potentially improve the patient compliance.

Design And Optimization Of Doxorubicin Hcl Proniosomes By-Design Of Experiment

Objective: The present research work was designed to formulate and optimize doxorubicin HCl proniosomes by design of experiment (DoE). Methods: A 4-factor, 3-level Box-Behnken design was used to explain multiple linear regression analysis and contour 3D plot responses. The independent variables selected were tween 20, cholesterol, hydration volume and sonication time; dependent variables percentage entrapment efficiency (PEE), mean vesicle size (MVS). Based on the Box-Behnken design 29 trial runs were studied and optimized for PEE and MVS. Further "Model F-Value" was calculated to confirm the omission of insignificant terms from the full-model equation to derive a multiple linear regression analysis to predict the PEE and MVS of niosomes derived from proniosomes. 3D plots were constructed to show the influence of independent variables on dependent variables. Results: PEE of doxorubicin HCl proniosomes was found to be in the range of 40.21-87.5%. The polynomial equation for PEE exhibited a good correlation coefficient (0.5524) and the "Model F-Value" of 7.41 implies the model is significant. P-values less than 0.0500 indicate model terms are significant. The MVS of doxorubicin HCl proniosomes was found to be in the range of 325.2 nm to 420.25 nm. The mathematical model generated for MVS (R2) was found to be significant with model F-value of 54.22. There is only a 0.01% chance that a "Model F-Value" this large could occur due to noise (P<0.0500) and R2 value of 0.9004. Conclusion: The DoE of Box-Behnken design demonstrated the role of the derived equation, 3D plot in predicting the values of dependent variables for the preparation and optimization of doxorubicin HCl proniosomes. The results suggest that doxorubicin HCl proniosomes can act as a promising carrier.

The Newly Developed Highly Sensitive Method For The Determination Of Capecitabine By Using Uv-Spectroscopy

Capecitabine is a fluoropyrimidine carbamate, designed as 'pro-drug' to the cytotoxic agent 5-fluorouracil (5-FU) meant to be administered orally. Capecitabine is used as first line monotherapy for metastatic colorectal cancer. In the present study simple, rapid, accurate UV spectrophotometric methods were developed and validated for the estimation of capecitabine in bulk and its formulations as per ICH guidelines. Three solvent systems viz., 0.1N NaOH, 0.1N HCl and Methanol: Water (1:3) were tried. The results suggest that the developed methods shows linearity over the concentration range of 2-24μg/ml with a correlation coefficient of 0.9999. All the developed methods were statistically validated for accuracy, precision, linearity, robustness, and ruggedness as per ICH guidelines. The % RSD values for validated methods were found to be less than 1.5 and methods will find application in routine analysis of drug formulations containing capecitabine.

2-amino-6-chlorobenzothiaozole as effective corrosion inhibitor for copper in acidic media / 国际药学研究杂志

This research is studied effect of "2-amino-6-chlorobenzothiaozole as effective corrosion inhibitor for copper in acidic media" by using weight Loss and polarization methods. Acid used is HCl, temperatures conditions varied between 45-65 oC and concentrations of inhibitors within range 100-250 ppm.Results showed that "2-amino-6-chlorobenzothiaozole "is good inhibitor for copper metal, and increasing the efficiency of inhibition of the process thus decrease both the potential and current density, lead to increased surface coverage of corrosion inhibitor. The reason for the good adsorption of the inhibitor is the presence of groups of nitrogen and sulfur in the structural composition of this type of inhibitor and production film layer. The study is study effects of the inhibitor on thermodynamics kinetic parameters ΔS, Ea, Δ Gads and ΔH.

Psychometric Properties of the Hypomania Checklist-32 in Korean Patients with Mood Disorders

OBJECTIVE: The aim of this study was to examine the validity of the Korean version of the Hypomania Checklist-32, second revision (HCL-32-R2) in mood disorder patients. METHODS: A total of 454 patients who diagnosed as mood disorder according to Structured Clinical Interview for DSM-IV Axis I Disorders, clinician version (SCID-CV) (bipolar disorder [BD] I, n=190; BD-II, n=72; and major depressive disorder [MDD], n=192) completed the Korean module of the HCL-32-R2 (KHCL-32-R2). RESULTS: The KHCL-32-R2 showed a three-factorial structure (eigenvalue >2) that accounted for 43.26% of the total variance. Factor 1 was labeled “active/elated” and included 16 items; factor 2, “irritable/distractible” and included 9 items; and factor 3 was labeled “risk-taking/indulging” and included 9 items. A score of 16 or more on the KHCL-32-R2 total scale score distinguished between BD and MDD, which yielded a sensitivity of 70% and a specificity of 70%. MDD and BD-II also could be differentiated at a cut-off of 15 with maximized sensitivity (0.67) and specificity (0.66). Cronbach’s alpha of KHCL-32-R2 and its subsets (factors 1, 2, and 3) were 0.91, 0.89, 0.81 and 0.79, respectively. Correlations between KHCL-32-R2 and Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale and Korean version of Mood Disorder Questionnaire were −0.66 (p=0.41), −0.14 (p=0.9), and 0.61 (p < 0.001), respectively. CONCLUSION: The KHCL-32-R2 may be a useful tool in distinguishing between bipolar and depressive patients in clinical settings.

Cardiac electrophysiological effect of (S)-OTS·HCl, a derivative of Baogongteng A / 上海交通大学学报（医学版）

Objective · To study the electrophysiological effect of (S)-OTS·HCl on the heart. Methods · The conventional intracellular recording, electrocardiograph (ECG) and Langendorff cardiac perfusion technique were employed to investigate the effect of (S)-OTS·HCl on in-vivo and in-vitro hearts of guinea pigs and rabbits. Results · (S)-OTS·HCl could bind to M2 muscarinic receptors and dose-dependently prolong the RR intervals significantly in vivo. It had no effect on resting potential (RP), action potential amplitude (APA), and maximum upstroke velocity of phase 0 (Vmax) of ventricular myocytes. Instead, 1×10-5 mol/L (S)-OTS·HCl could shorten the action potential duration at 50 percent repolarization (APD50) and APD90 to 91.6% and 90.9%, respectively. And the spontaneous depolarization rate of phase 4 (SDR) of sinus nodes was reduced to its 13.7% when rabbit sinus nodes were exposed to 1×10-7 mol/L (S)-OTS·HCl. (S)-OTS·HCl could inhibit Ca2+channel effectively. It decreased APA and Vmax of sinus nodes and attenuated the cardiac contractility in vitro. Conclusion · (S)-OTS·HCl is a potent cholinergic agonist and has negative chronotropic, dromotropic, and inotropic effects on hearts via binding to M2 muscarinic receptors.

Lung adenocarcinoma treated by Erlotinib HCL Tablets and chemotherapy combined with bevacizumab after drug resistance: A case report and literature review / 吉林大学学报(医学版)

Objective:To report a case of lung adenocarcinoma of stage Ⅳ with epidermal growth factor receptor (EGFR) mutation treated by Erlotinib HCL Tablets and chemotherapy combined with bevacizumab after drug resistance,and to review the related literatures.Methods:A female patient without smoking history was diagnosed with lung adenocarcinoma (stage cT3N2M1 Ⅳ) with metastatic lesions in liver and bones by chest CT,lung puncture biopsy,and whole-body PET-CT.EGFR gene test reported mutation (19 del).Through treatment of overall survival,pemetrexed disodium for injection plus carboplatin injection,gemcitabine hydrochloride for injection plus cisplatin injection,paclitaxel for injection (albumin bound) single and with bevacizumab;the overall survival (OS) was assessed as 32 months.And the period of Erlotinib HCL Tablets showed 10 months of progressive-free survival (PFS).However,due to the metastatic lesions that suppressed biliary system in liver,hyperbilirubinemia emerged (total bilirubin 304 μmol · L-1,direct bilirubin 193 μmol · L-1).Bevacizumab was adopted and the syndrome relieved (total bilirubin 70 μmol · L-1,direct bilirubin 35 μmol · L-1),yielding three months of PFS.But the bilirubin level upgraded with total bilirubin of 908 μmol · L-1.The patient died because of hyperbilirubinemia.Results:10-month PFS occupied 1/3 of OS was acquired in the patients with EGFR-mutated lung adenocarcinoma (stage Ⅳ) after treated with Erlotinib HCL Tablets.Chemotherapy combined with bevacizumab acquired 3 months of PFS after hyperbilirubinemia emerged with drug resistance and multi-lines of chemotherapy.Conclusion:EGFR-TKIs are effective in treatment of lung adenocarcinoma with EGFR mutation;bevacizumab can inhibit the formation of vessels by targeting on VEGF under the circumstance of multiple drug resistance.Therefore,chemotherapy combined with bevacizumab can be used as the fifth-line of therapy in dealing with the hyperbilirubinemia induced by lung adenocarcinoma with liver metastasis.

Lung adenocarcinoma treated by Erlotinib HCL Tablets and chemotherapy combined with bevacizumab after drug resistance: A case report and literature review / 吉林大学学报(医学版)

Objective:To report a case of lung adenocarcinoma of stage Ⅳ with epidermal growth factor receptor (EGFR) mutation treated by Erlotinib HCL Tablets and chemotherapy combined with bevacizumab after drug resistance,and to review the related literatures.Methods:A female patient without smoking history was diagnosed with lung adenocarcinoma (stage cT3N2M1 Ⅳ) with metastatic lesions in liver and bones by chest CT,lung puncture biopsy,and whole-body PET-CT.EGFR gene test reported mutation (19 del).Through treatment of overall survival,pemetrexed disodium for injection plus carboplatin injection,gemcitabine hydrochloride for injection plus cisplatin injection,paclitaxel for injection (albumin bound) single and with bevacizumab;the overall survival (OS) was assessed as 32 months.And the period of Erlotinib HCL Tablets showed 10 months of progressive-free survival (PFS).However,due to the metastatic lesions that suppressed biliary system in liver,hyperbilirubinemia emerged (total bilirubin 304 μmol · L-1,direct bilirubin 193 μmol · L-1).Bevacizumab was adopted and the syndrome relieved (total bilirubin 70 μmol · L-1,direct bilirubin 35 μmol · L-1),yielding three months of PFS.But the bilirubin level upgraded with total bilirubin of 908 μmol · L-1.The patient died because of hyperbilirubinemia.Results:10-month PFS occupied 1/3 of OS was acquired in the patients with EGFR-mutated lung adenocarcinoma (stage Ⅳ) after treated with Erlotinib HCL Tablets.Chemotherapy combined with bevacizumab acquired 3 months of PFS after hyperbilirubinemia emerged with drug resistance and multi-lines of chemotherapy.Conclusion:EGFR-TKIs are effective in treatment of lung adenocarcinoma with EGFR mutation;bevacizumab can inhibit the formation of vessels by targeting on VEGF under the circumstance of multiple drug resistance.Therefore,chemotherapy combined with bevacizumab can be used as the fifth-line of therapy in dealing with the hyperbilirubinemia induced by lung adenocarcinoma with liver metastasis.

Inclusion complex of amiodarone hydrochloride with cyclodextrins: preparation, characterization and dissolution rate evaluation

ABSTRACT This study aimed to improve the water solubility of amiodarone hydrochloride (AMH) via inclusion complexes with β-cyclodextrin, methyl-β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin. Inclusion complexes were developed by physical mixture, coevaporation, spray-drying and freeze-drying. Solid state analysis was performed using X-ray powder diffraction, differential scanning calorimetry and scanning electronic microscopy. Thermodynamic studies demonstrate that the inclusion complexes of drug into different cyclodextrins were an exothermic process that occurred spontaneously. Water solubility and drug dissolution rates were significantly increased after the formation of inclusion complexes with the cyclodextrins evaluated in relation to the physical mixture and pure drug. The present study provides useful information for the potential application of complexation with amiodarone HCl. This may be a good strategy for the development of solid pharmaceutical dosage forms.

Development of a new single unit dosage form of propranolol HCl extended release non-effervescent floating matrix tablets: In vitro and in vivo evaluation.

The objective of the present investigation was to develop extended release non-effervescent floating matrix tablets of Propranolol Hydrochloride (PPH) to extend the gastric residence time (GRT) and prolong the drug release after oral administration. Different viscosity grades of Hydroxypropyl methylcellulose (HPMC) polymers such as HPMC K4M, HPMC K15M and HPMC K100M were used as drug release retardants. Glyceryl behinate (Compritol 888 ATO) and Glyceryl monosterate (Precirol ATO 5) were used as low density lipids in order to get the desired buoyancy over a prolonged period of time. The drug excipients compatibility study was carried out by using Differential Scanning Calorimetry (DSC). All the formulations were prepared by direct compression technique. The prepared tablets were evaluated for their physical characters, in vitro drug release and in vitro buoyancy. The release and floating property depends on the polymer type, polymer proportion, lipid type and lipid proportions. The drug release profiles of all the formulations were subjected to Zero order, First order, Higuchi and Peppas kinetic models, and the optimized formulation (F7) followed the Peppas model (R2= 0.987) with non-Fickian diffusion mechanism(n>0.5). The optimized formulation was subjected for in vivo radiographic studies in healthy human volunteers (n=3). These studies revealed a mean gastric residence time of 5±1.73 h (n=3).

Comparison of the response using ICR mice derived from three different sources to ethanol/hydrochloric acid-induced gastric injury / 한국실험동물학회지

Animal models for gastric ulcers produced by physical, pharmacological and surgical methods have been widely employed to evaluate therapeutic drugs and investigate the mechanism of action of this disease. ICR mice were selected to produce this model, even though several mice and rats have been widely used in studies of gastric ulcers. To compare the responses of ICR mice obtained from three different sources to gastric ulcer inducers, alterations in gastric injury, histopathological structure, and inflammation were measured in Korl:ICR (Korea NIFDS source), A:ICR (USA source) and B:ICR (Japan source) treated with three concentrations of ethanol (EtOH) (50, 70, and 90%) in 150 mM hydrochloric acid (HCl) solution. Firstly, the stomach lesion index gradually increased as the EtOH concentration increased in three ICR groups. Moreover, a significant increase in the level of mucosal injury, edema and the number of inflammatory cells was similarly detected in the EtOH/HCl treated group compared with the vehicle treated group in three ICR groups. Furthermore, the number of infiltrated mast cells and IL-1β expression were very similar in the ICR group derived from three different sources, although some differences in IL-1β expression were detected. Especially, the level of IL-1β mRNA in 50 and 90EtOH/HCl treated group was higher in Korl:ICR and A:ICR than B:ICR. Overall, the results of this study suggest that Korl:ICR, A:ICR and B:ICR derived from different sources have an overall similar response to gastric ulcer induced by EtOH/HCl administration, although there were some differences in the magnitude of their responses.