Study on the quality standard of Kuipingning gastric floating tablets / 中国药房

OBJECTIVE To establish the quality standard of Kuipingning gastric floating tablets. METHODS Kuipingning gastric floating tablets were prepared and investigated in terms of property ，weight difference and friability. Crydalis yanhusuo was identified qualitatively by thin layer chromatography （TLC）method. High performance liquid chromatography method was used to determine the content of total anthraquinones in Rheum palmatum ，and set the content limit of total anthraquinones. The floating performance and release degree of the preparation were investigated ，and the release kinetic process was fitted. RESULTS Kuipingning gastric floating tablets prepared in this study were gray white to gray tablets with slight smell and bitter taste ；the weight difference and friability were all in line with relevant regulations ；the established TLC method possessed strong specificity and could accurately identify C. yanhusuo . The average content of total anthraquinones in R. palmatum was 17.95 mg/tablet，and its content limit would not be less than 14.36 mg/tablet. The initial floating time of the preparation was no more than 10 s，and the holding time was more than 8 h. The release kinetics process accorded with the Retger-Peppas release model. CONCLUSIONS The method established in this study shows good reliability ，stability and feasibility ，and can effectively control the quality of Kuipingning gastric floating tablets.

Formulation, Optimization, in vitro and in-vivo evaluation of levofloxacin hemihydrate Floating Tablets

Abstract The objective of the present investigation was to design, optimize and characterize the gastro retentive floating levofloxacin tablets and perform in-vivo evaluation using radiographic imaging. The floating tablets were prepared by using polymers i.e hydroxy propyl methyl cellulose (HPMC-K4M) and carbopol-940 individually and in combination by nonaquous granulation method. All the Formulations were evaluated for swelling index (S.I), floating behavior and in-vitro drug release kinetics. The compatibility study of levofloxacin with other polymers was investigated by FTIR, DSC, TGA and XRD. Results from FTIR and DSC revealed no chemical interaction amongst the formulation components. The optimized formulation (F11) showed floating lag time (FLT), total floating time (TFT) swelling index (S.I) of 60 sec, >16h and approximately 75 %, respectively. Moreover, F11 showed zero order levofloxacin release in simulated gastric fluid over the period of 6 h. X-ray studies showed that total buoyancy time was able to delay the gastric emptying of levofloxacin floating tablets in rabbits for more than 4 hours. In conclusion the optimized formulation (F11) can be used for the sustained delivery of levofloxacin for the treatment of peptic ulcer.

Formulation And In-Vitro Evaluation Of Theophylline Hydrochloride Effervescent Floating Tablets: Effect Of Polymer Concentration On Tablet Buoyancy

Objective: This study was undertaken to formulate a floating drug delivery system of theophylline hydrochloride using different concentrations of a chosen polymer and then investigate how polymer concentration affects buoyancy and drug release properties of the tablets. Methods: Hydroxypropyl methylcellulose (HPMC) at different concentration levels of 15% (F1), 20% (F2) and 30% (F3) was used to form the three formulation batches of floating tablets. Wet granulation method was used for the granule preparation while Sodium bicarbonate and citric acid were used as the gas generating agent. The physical properties of the granules and the floating tablets were evaluated. Also determined were the physicomechanical properties, buoyancy and swelling characteristics of the tablets. The in vitro drug release study was carried out according to the USP I (basket method) for 8h in 900 ml 0.1N HCl at 50 rpm. Samples withdrawn at the regular predetermined time were analyzed spectrophotometrically at a wavelength of 271 nm and data obtained statistically analyzed by one-way analysis of variance (ANOVA). The differences between means were considered significant at P<0.05. Results: The result showed that polymer (HPMC) concentration significantly (p>0.05) increased swelling index and improved floating lag time, it had no significant effect on the total floating time. Percentage drug release at the end of 8 h was 100%, 98.2% and 96.13% for formulation F1, F2 and F3, respectively. All three formulations followed the Higuchi drug release kinetics model and the mechanism of drug release was the non Fickian diffusion with exponents of 0.46, 0.51 and 0.56 for the respective batch. Conclusion: Batch F3 gave a better-controlled drug release and floating properties in comparison to batch F1 and F2 thus Polymer concentration influenced the onset of floating and controlled the release of Theophylline.

Preparation and Quality Evaluation of Gastric Floating Tablets of Schisandra chinensis Total Lignans / 中国药房

OBJECTIVE：To study the prepar ation technology of gastric floating tablets of Schisandra chinensis total lignans （SCTL），and evaluate the quality of prepared tablets. METHODS ：Based on single factor test ，the orthogonal experiment was conducted to optimize the formulation of SCTL gastric floating tablets with the contents of hydroxypropylmethylcellulose （HPMC） K15M，NaHCO3 and microcrystalline cellulose as the factors ，using starting time ，holding time and cumulative release rate of gastric floating tablets as evaluation indexes. The properties ，weight difference ，floatability and accumulative release rate of the prepared SCTL gastric floating tablets were determined. The gastric floating tablets were qualitatively identified by TLC ，and the contents of schisandrin A and total lignans were determined by HPLC and UV spectrophotometry. RESULTS ：The optimal formulation of SCTL gastric floating tablets was made up of 23％ SCTL extract ，20％ HPMC K 15M，40％ microcrystalline cellulose，15％ sodium bicarbonate ，1％ octadecyl alcohol and 1％ polyvinylpyrrolidone. The results of detection of this preparation were in line with the related provisions of “0101 tablet”stated in 2015 edition of Chinese Pharmacopoeia （part Ⅳ）. TLC indicated that the chromatogram of the test sample showed the main spots of same color as the corresponding positions of the chromatogram of schizandrol A control ，Schisandra chinensis reference substance and raw material ，while the negative control has no interference. Content determination results shows that the average content of schizandrol A and total lignans in SCTL gastric floating tablets is 3.187，19.617 mg. It was preliminarily formulated that the content limitation of schizandrol A in one tablet should not be less than 2.50 mg，and the content of total lignans （calculated by schizandrol A ）should not be less than 15.50 mg. CONCLUSIONS：The preparation technology of SCTL gastric floating tablets is stable ，feasible and controllable in quality.

In-vitro and In-vivo Relationship of Gabapentin from Floating and Immediate Release Tablets

Gabapentiniseffectiveagainst post-traumaticspinalinjury-inducedneuropathicpain.Itrequireshighdosageand frequency inthemanagementofneuropathicpain.Thepresentresearchworkwasanattempttoformulate andevaluategabapentingastro-retentivetabletstoprolonggastricresidenceandincreasedrug absorptionand furtherincreasebioavailability.Thefloatingtabletsofgabapentinwerepreparedintwodoses(300and600mg) byusingtwopolymers(hydroxylpropylmethylcelluloseandhydroxylpropylcellulose).Immediaterelease tabletsofgabapentincontaining thesamedoseswerepreparedandusedasreferenceformulations.The physicochemicalcharacteristicsofthepreparedtabletsweredetermined(drug content,weightvariation,friability, hardness,thicknessand diameter). Drugreleasefromthepreparedtabletswasfollowed and foundthatby increasingdrug concentrationinthetabletsreleaserateincreases.Floatingtabletsshowedprolongeddrugrelease (over96%)tomorethan15hrs.Immediatereleasetabletsshowedover97%drugreleasewithin48min.In-vivoresultsshowedthatplasmaexposuretogabapentininanimalsreceivingthedrug doesnotdose proportionalandtherefore maynotreachtherapeuticallyusefullevels.AUC0-24andCmaxincaseof300mgtabletsaremorethanthoseincaseof 600 mgtablets.Thein-vivo releaseofgabapentin doesnot correlatewiththein-vitroreleaseofthedrug.

Pharmacodynamics and mechanism of Shaoyao Gancao Intragastric Floating Tablets based on unification of medicines and excipients / 中草药

Objective: To study the pharmacodynamic effect of “unification of medicines and excipients” and the mechanism of action about Shaoyao Gancao Intragastric Floating Tablets (SGIFT). Methods: Rabbits were randomly divided into control group and model group, Shenmei Yangwei Granule group (1.0 g/kg), Shaoyao Gancao Decoction extract group (1.0 g/kg), low-dose SGIFT group (1.0 g/kg), high-dose SGIFT group (1.5 g/kg), chitosan blank excipients group (1.0 g/kg). The acute gastric ulcer model was established in the blank excipient group without chitosan (1.0 g/kg). Six rats in each group, fasting for 24 h after 13 d of continuous administration, and gastric administration of anhydrous ethanol (2.5 mL/single). The blood and gastric tissue were taken out after 1.5 h to observe the pathological damage in each group. The expression of GAS, MDA, PG, epidermal growth factor (EGF) in serum and EGF, PGE2, TFF1 in gastric tissue of each group were detected. Results: Compared with the model group, the other groups can improve the gastric histopathology of rabbits with acute gastric ulcer effectively. The content of EGF in serum and EGF, PGE2, and TFF1 in gastric tissue of rabbits was increased in varying degrees, and the content of GAS, MDA, and PG in serum was all decreased in different degrees. Conclusion: SGIFT had certain therapeutic effects on rabbits with anhydrous ethanol gastric ulcer. The mechanism might be related to protecting gastric mucosa, increasing the content of protective factors, and reducing the content of attack factors.

Repair effect of brain protein hydrolysate on H2O2-induced oxidative damage in PC12 cells and optimization of formulation of its stomach floating tablets / 吉林大学学报(医学版)

Objective:To detect the repair effect of brain protein hydrolyzate(BPH)on the oxidative damage induced by H2O2in the PC12 cells,and to optimize the prescription of BPH stomach floating tablets using the star design effect surface method.Methods:The PC12 cells in the logarithmic phase were divided into normal control group,model group(300 μmol·L-1H2O2),BPH group,artificial gastric juice-treated BPH(GBPH)group, artificial intestinal juice-treated BPH(IBPH)group,artificial gastric juice-treated BPH tablets(GBPH-T)group and artificial gastric juice-treated BPH floating tablets(GBPH-FT)group(The latter five groups were added with 20,40,60,80 and 100 mg·L-1BPH treated with different conditions);at the same time blank control group was set up.The PC12 cells in normal control group didn't receive any treatment,the blank control group was added with medium only,and the PC12 cells in model group were treated with H2O2(300 μmol·L-1)for 3 h. The cell viability was detected by MTT assay.Using Design-expert 8.0.6 Trial software,the dosages of HPMC-K4M,octadecanol and acrylic resin Ⅱ were used as the investigation factors,and the 8 h cumulative release in vitro was used as the evaluation index to optimize the prescription.Results:Compared with normal control group, the activity of PCl2cells in 60 mg·L-1BPH group was increased(P<0.05).Compared with model group,the vitalities of PC12 cells in BPH group,IBPH group,GBPH group and GBPH-FT group were increased significantly (P<0.05 or P<0.01).Compared with BPH group,the cell viability in IBPH group was decreased significantly (P<0.05),and there was no significant difference in GBPH group(P>0.05).Compared with GBPH-T group, the cell viability in GBPH-FT group was significantly increased(P<0.05).The optimal prescription was BPH 20 mg,lactose 10 mg,magnesium stearate 0.4 mg,microcrystalline cellulose 20 mg,HPMC-K4M 27 mg, octadecanol 63 mg,acrylic resinⅡ13 mg;all floating tablets drift in 5 s and sustained floating > 8 h;the difference of the measured value of 8 h cumulative release and the predicted value was not statistically significant (P>0.05).Conclusion:BPH has a significant repair effect on the H2O2-induced oxidative damage in the PC12 cells.Star design-effect surface method has good predictability and reproducibility;it is reasonable and feasible, and can be used to optimize the prescription of BPH stomach floating tablets.

Repair effect of brain protein hydrolysate on H2O2-induced oxidative damage in PC12 clls and optimization of formulation of its stomach floating tablets / 吉林大学学报(医学版)

Objective: To detect the repair effect of brain protein hydrolyzate (BPH) on the oxidative damage induced by H2O2 in the PC12 cells, and to optimize the prescription of BPH stomach floating tablets using the star design effect surface method Methods: The PC12 cells in the logarithmic phase were divided into normal control group, model group 300 μmol · L-1 H2O2), BPH group, artificial gastric juice-treated BPH (GBPH) group, artificial intestinal juice-treated BPH (IBPH) group, artificial gastric juice-treated BPH tablets (GBPH-T) group and artificial gastric juice-treated BPH floating tablets (GBPH-FT) group (The latter five groups were added with 20, 40, 60, 80 and 100 mg · L-1 BPH treated with different conditions); at the same time blank control group was set up. The PC12 cells in normal control group didn't receive any treatment, the blank control group was added with medium only, and the PC12 cells in model group were treated with H2O2 300 μmol · L-1) for 3 h. The cell viability was detected by MTT assay. Using Design-expert 8.0.6 Trial software, the dosages of HPMC-K4M, octadecanol and acrylic resin E were used as the investigation factors, and the 8 h cumulative release in vitro was used as the evaluation index to optimize the prescription. Results: Compared with normal control group, the activity of PC12 cells in 60 mg · L-1 BPH group was increased (P0.05). Compared with GBPH-T group, the cell viability in GBPH-FT group was significantly increased (P 8 h; the difference of the measured value of 8 h cumulative release and the predicted value was not statistically significant (P>0.05). Conclusion: BPH has a significant repair effect on the H2O2-induced oxidative damage in the PC12 cells. Star design-effect surface method has good predictability and reproducibility; it is reasonable and feasible, and can be used to optimize the prescription of BPH stomach floating tablets.

Preparation and release mechanism of tectorigenin intragastric floating sustained-release tablets / 中国中药杂志

To investigate the preparation technology and release mechanism of tectorigenin intragastric floating sustained-release tablets. The tablet was produced by wet granulation compression method, with hydroxypropyl methyl cellulose (HPMCK15M), cross-linked polyvinyl pyrrolidone (PVPP), octadecanol and sodium bicarbonate as excipient. The prescriptions were screened and optimized by orthogonal experimental design with in vitro floating capacity and drug release characteristics as the evaluation indexes. The optimization results were as follows: tectorigenin 33.3%, HPMCK15M 16.7%, PVPP 20.0%, octadecanol 13.3%, sodium bicarbonate 5%, and starch gel 10.7%. The prepared tablet can be floated within 10 s in the artificial gastric juice, lasting for 12 h in vitro, with a cumulative release rate of 70% in 10 h. The analysis of Rritger-Peppas equation showed that the sustained-release tablet had two advantages of both drug diffusion and skeleton dissolution. The tablet had good appearance and compressibility, as well as favorable floating capacity and drug release characteristics.

Study on Bioequivalence of Levodopa Micro-capsule Floating Tablets in Beagle Dogs after Multi-dose Ad-ministration / 中国药房

OBJECTIVE:To study the bioequivalence of Levodopa micro-capsule floating tablets in Beagle dogs after multi-dose administration. METHODS:6 dogs were collected and divided into Levodopa micro-capsule floating tablets group and Com-pound levodopa preparation group (Benserazide tablet,reference preparation). They were given levodopa 200 mg intragastrically, every 8 h,for consecutive 4 day. In two-period crossover test,HPLC method was established to determine the concentration of le-vodopa in dog. The pharmacokinetic parameter,bioequivalence and plasma concentration fluctuation of steady state were calculated. RESULTS:The main pharmacokinetic parameters of Levodopa micro-capsule floating tablets and reference preparation were as that cmax were(4.23±0.75)and(8.47±1.18)μg/ml;AUC0-∞ were(12.18±1.16)and(13.81±2.12)μg·h/ml;tmax were(1.83±0.26) and(0.67±0.13)h,respectively. 90% confidence intervals for the geometric mean ratio of AUC0-∞ for test and reference prepara-tion were 80.61%-97.90%,and that for cmax were 42.75%-57.63%,respectively. There was statistical significance in tmax between test and reference preparation. Degree of fluctuation of test and reference preparation at steady state were(283.914±43.217)% and (506.489±78.965)%,and fluctuation coefficient were(177.463±7.873)% and(187.405±1.650)%,respectively. The degree of fluctuation of test preparation was significantly less than that of reference preparation. CONCLUSIONS:Levodopa micro-capsule floating tablets show good sustained-release property,and are bioequivalent with reference preparation in absorption after multiple dose administration. It also has lesser fluctuation of blood concentration.

Formula Optimization of Levodopa Microcapsules Floating Tablets / 中国药师

To optimize the formula of levodopa microcapsules floating tablets. Methods:The contents of levodopa and benserazide in the microcapsules floating tablets were determined by HPLC simultaneously. The release rate as the index, an orthogonal design was used to optimize the formula and preparation technology of levodopa microcapsules floating tablets. The release property of the microcapsules floating tablets was evaluated. Results:The HPLC method for the in vitro determination of levodopa and benserazide in the floating tablets met the methodological requirements. The selected formula was as following:the amount ratio of stearic acid, the drugs, acrylic resin and HPMC was 2∶5∶2∶1. The average weight of the tablets was 550 mg. The results of validated tests showed that the microcapsules floating tablets had floating and sustained release property, which could be used by divided dose. Conclusion: The optimized formula of the microcapsules floating tablets is reasonable, and the production process is stable and feasible.

Formulation of gastroretentive floating drug delivery system using hydrophilic polymers and its in vitro characterization

The aim of the present research is to formulate and evaluate the gastroretentive floating drug delivery system of antihypertensive drug, propranolol HCl. Gastroretentive floating tablets (GRFT) were prepared by using a synthetic hydrophilic polymer polyethylene oxide of different grades such as PEO WSR N-12 K and PEO 18 NF as release retarding polymers and calcium carbonate as gas generating agent. The GRFT were compressed by direct compression strategy and the tablets were evaluated for physico-chemical properties, in vitro buoyancy, swelling studies, in vitro dissolution studies and release mechanism studies. From the dissolution and buoyancy studies, F 9 was selected as an optimized formulation. The optimized formulation followed zero order rate kinetics with non-Fickian diffusion mechanism. The optimized formulation was characterised with FTIR studies and observed no interaction between the drug and the polymers.

O objetivo da presente pesquisa é o de formular e avaliar o sistema de liberação de fármaco gastrorretentivo flutuante, contendo o anti-hipertensivo, cloridrato de propranolol. Comprimidos gastrorretentivo flutuantes (GRFT) foram preparados utilizando um polímero hidrofílico sintético, o óxido de polietileno, de diferentes graus, tais como GE WSR N-12 K e GE 18 NF, como polímeros de retardamento de liberação, e carbonato de cálcio, como agente gerador de gases. Os GRFT foram comprimidos por compressão direta e avaliados para determinação das propriedades físico-químicas, flutuabilidade in vitro, estudos de inchamento, de dissolução in vitro e de mecanismo de liberação. Dos testes de dissolução e de flutuabilidade, selecionou-se F 9 como formulação otimizada. A formulação otimizada seguiu cinética de ordem zero, com mecanismo de difusão não-Fickiano. Essa formulação foi caracterizada por estudos de FTIR, não se observando interação entre o fármaco e os polímeros.

Formulation and characterization of gastroretentive drug delivery system of losartan potassium.

Floating matrix tablets of losartan potassium were developed with an aim to prolong its gastric residence time and increase the bioavailability of drug. Rapid gastrointestinal transit could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy of the administered dose. The tablets were prepared by wet granulation technique, using polymers Methocel K15 and Methocel K100 in combination with other standard excipients. Sodium bicarbonate was incorporated as gas generating agent. The effects of sodium bicarbonate and polymers on drug release profile and floating properties were investigated. It was found that viscosity of Methocel K15 and Methocel K100 along with sodium bicarbonate had significant impact on the release and floating properties of the delivery system. The decrease in the release rate was observed with an increase in the viscosity of the polymeric system. Polymer with high viscosity Methocel K100 was shown to be beneficial than low viscosity polymer Methocel K15 in improving the floating properties of gastric floating drug delivery system (GFDDS). The observed difference in the drug release and floating properties of GFDDS could be attributed to the difference in the basic properties of two polymers, Methocel K15 and Methocel K100 due to their water uptake potential and functional group substitution. The release mechanism were explored and described with zero-order, first-order and Korsmeyer-Peppas equations. The drug release profiles and buoyancy of the floating tablets were stable when stored at 40°C/75% RH for 6 months.

Formulation and Evaluation of Gastroretentive Floating Tablets of Domperidone Maleate.

The low bioavailability (15%) and good solubility of Domperidone Maleate in acidic pH following oral administration favours development of a gastro retentive formulation. Gastroretentive floating matrix tablets of Domperidone Maleate were successfully prepared with hydrophilic polymers like HPMC K4M, HPMC K15M and HPMC K100M. From the Preformulation studies for drug excipients compatibility it was observed that there was no compatability problem with the excipients used in study. The drug release from most of the formulations follows fickian diffusion. From in-vivo X-ray studies, it was clearly observed that the floating tablets showed a gastric residence of nearly 4.5 hrs in fed state.

Formulation and characterization of gastroretentive drug delivery system of losartan potassium.

Floating matrix tablets of losartan potassium were developed with an aim to prolong its gastric residence time and increase the bioavailability of drug. Rapid gastrointestinal transit could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy of the administered dose. The tablets were prepared by wet granulation technique, using polymers Methocel K15 and Methocel K100 in combination with other standard excipients. Sodium bicarbonate was incorporated as gas generating agent. The effects of sodium bicarbonate and polymers on drug release profile and floating properties were investigated. It was found that viscosity of Methocel K15 and Methocel K100 along with sodium bicarbonate had significant impact on the release and floating properties of the delivery system. The decrease in the release rate was observed with an increase in the viscosity of the polymeric system. Polymer with high viscosity Methocel K100 was shown to be beneficial than low viscosity polymer Methocel K15 in improving the floating properties of gastric floating drug delivery system (GFDDS). The observed difference in the drug release and floating properties of GFDDS could be attributed to the difference in the basic properties of two polymers, Methocel K15 and Methocel K100 due to their water uptake potential and functional group substitution. The release mechanism were explored and described with zero-order, first-order and Korsmeyer-Peppas equations. The drug release profiles and buoyancy of the floating tablets were stable when stored at 40°C/75% RH for 6 months.

Dual acting oral floating matrix tablets of ranitidine hydrochloride.

The main purpose of this work was to prepare floating matrix drug delivery system of Ranitidine. Floating matrix tablets of Ranitidine were developed to prolong gastric residence time and increase its bioavailability. Rapid gastrointestinal transit could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy of the administered dose. Floating matrix tablets containing 100 mg Ranitidine were developed using different effervescent salts and polymer combinations. The tablets were prepared by direct compression technique, using polymers such as hydroxyl propyl methyl cellulose (HPMC K4M), Carbopol 934 in combination. Sodium bicarbonate, citric acid, calcium carbonate was incorporated as a gas-generating agent. The effects of sodium bicarbonate on drug release profile and floating properties were investigated. The formulation was optimized on the basis of acceptable tablet properties, floating lag time, total duration of floating and in vitro drug release. The formulated tablets with optimum hardness, uniform thickness, consistent weight uniformity and low friability. The results of dissolution studies, floating lag time indicated that formulations F4 exhibited good and controlled drug release. Applying the linear regression analysis and model fitting showed the selected formulation F4 showed diffusion coupled with erosion drug release mechanism, followed first order kinetics. Optimized floating matrix tablets F4 showed no change in physical appearance, drug content, or in dissolution pattern after storage at 250C/ relative humidity 65% and 40°C / relative humidity 75% for a period of 3 months.

Design and evaluation of levofloxacin hemihydrate floating tablets.

In the present study, the tablets were prepared by melt granulation method, using the polymer, hydroxy propyl methyl cellulose (HPMC K100M) with different amounts and other excipients and sodium bicarbonate as gas generating agent. The present study is to develop a floatable drug delivery system of Levofloxacin hemihydrate for sustained drug delivery and gastric retentive property with special emphasis on optimization of formulations for floating matrix tablets. Thus the study aims to improve the oral bioavailability of the drug and to achieve extended retention in the stomach which may result in prolonged absorption. Tablets were evaluated by different parameters such as weight uniformity, content uniformity, thickness, hardness, IR spectral analysis, in vitro release studies, Buoyancy determination and kinetic analysis of dissolution data, stability studies Levofloxacin floating tablet drug delivery system showed improved in-vitro bioavailability and extended drug release which may favour the reduced dose frequency and patient compliance.