Study of Sustained Release Phenylpropanolamine Hydrochloride Hydrophilic Matrix Tablets Containing Hydroxypropylmethylcellulose K100M and Carbopol 971P

选用HPMC K100M和卡波普971P为骨架材料，粉末直接压片法制备骨架片，考察释放度，反相高效液相色谱法检测盐酸苯丙醇胺（PPA·HCl）的浓度。释药曲线均符合Higuchi方程（R＞0．98，P＜0．01）。运用正交设计法，以美国市场的PPA·HCl缓释片Acutrim^R为对照，相似因子f2值为指标，筛选获得了最优处方。其工艺重现性合格。研制片在0．1mol·L^-1 HCl,H2O(pH6.5)，磷酸盐缓冲液（PBS）pH5.0,6.8和7.4的介质中，以及在0.1mol·L^-1HCl中释放2h，转移至PBS6．8中释放10h，相对于对照品的f2值为63－74，表明在各介质中两制剂的释药曲线相似。释药影响因素的考察结果表明：在本实验考察的范围内，骨架片在水中的释药速率与HPMC K100M和卡波普971P的用量呈负相关。HPMC K100M和卡波普971P的比例（保持聚合物总用量相同），硬脂酸镁量和骨架片硬度对释药速率无显著性影响。

Pharmacokinetics of Moclobemide Sustained Release Tablets after Multiple Oral Dose Administration in Healthy Volunteers

To investigate the pharmacokinetic characteristics of moclobemide sustainedrelease tablets after multiple oral dose administration in healthy Chinese volunteers. MethodsMoclobemide sustained release tablets were given as a multiple oral dose regimen of 300 mg oncedaily for five consecutive days to 12 healthy volunteers. The concentrations of moclobemide inplasma were determined by reversed-phase high performance liquid chromatography. The partialpharmacokinetic parameters were calculated using 3p97 pharmacokinetic program. Results Theconcentration-time profile fitted an one-compartment model best. The steady-state pharmacokineticparameters of moclobemide sustained release tablets after multiple oral doses were as follows:C_(max) was (1 950 +- 156) μg· L^(-1), T_(max) was (6.00 +-1.55) h, T_(1/2(kel)) was (3.14 +-0.12)h, AUC_(ss 0-24) was (22 836 +- 1 842) μg·h· L^(-1), MRT was (7.68+-0.36) h, CL/F_((s)) was(20.2+-2.1) L·h^(-1), and V/F_((c)) was (91.4+-9.4) L, respectively. No marked adverse events werenoted during this study. Conclusion The formulation has a sustained-release effect and goodtolerance in the healthy volunteers, which provides useful information for clinical practice.

Preparation and <i>in Vitro</i>Drug Release Evaluation of Once-Daily Metformin Hydrochloride Sustained-Release Tablets

The objective of this study was to develop once-daily metformin hydrochloride sustained-release tablets (MHSRT) and evaluate their in vitro release behavior. MHSRT were prepared by the film coating method. The in vitro drug release rate of MHSRT and the commercial tablets Fortamet? made in the United States of America in water was fitted with zero order kinetic equation, and Ritger-Peppas kinetic equation in 0.1 M HCl and pH 6.8-phosphate buffer, respectively. The similarity factor f2 values of MHSRT in three different dissolution medium were 82, 80 and 74, respectively in comparison with imported Fortamet?, which were all greater than 50. The results of storage-stability showed that MHSRT were stable for at least 6 months under stress condition (40℃ ± 2℃, RH 75% ± 5%). Therefore, in this study, MHSRT were successfully prepared using optimized formulation technologies that meet mass produce. The in vitro release behavior of MHSRT was almost similar to that of imported Fortamet?.

Application of D-Optimal Study Design with Contour Surface Response for Designing Sustained Release Gliclazide Matrix Tablets

An optimized formulation of a sustained release tablet of Gliclazide was developed. The use of Doptimal design with a polynomial statistical model to analyze dissolution data reduced the number of laboratory tests required to obtain an optimal dosage form. The final formulation contained 22 mg of Methocel&regE15LV, 16.5 mg Methocel&regE15 and 10.0 mg of Dibasic Calcium Phosphate per 30 mg Gliclazide sustained release tablet. Dissolution studies performed on tablets from 5000 tablet test batches released greater than 90 percent of loaded drug in eight hours. Drug release from the optimized tablets followed a pattern more closely similar to zero-order than other mechanisms of drug release tested. Storage of tablets in accelerated and ambient conditions for 6 and 12 months respectively did not alter any of the physico-chemical properties, drug release or the drug release rate compared to initial observations and dissolution data of the prepared tablets. The addition of potassium phosphate and monosodium phosphate to the tablet reduced the effect pH has on Gliclazide dissolution compared to the commercially available product.

Preparation and Pharmacokinetic Characterization of Sustained Release Melatonin Tablet

Aim To prepare the sustained release melatonin tablet with HPMC matrix and study its pharmacokinetics and bioavailatility. Methods HPMC was used as matrix to formulate the sustained release tablet. The influences of the size of melatonin, type and amount of HPMC, drug loading, type and amount of additives, and compressing pressure were investigated. Plasma concentration of melatonin in dogs after intravenous injection of two doses and oral administration of sustained release tablets and unmodified release capsules was detected by HPLC using fluorescence detector. Results The drug release from sustained release tablets was influenced by the size of melatonin, type and amount of HPMC, drug loading, and type and amount of additives. Melatonin was found to fit two compartment model after intravenous injection, AUC was proportional to doses, and t(1/2β) of two doses has no significant difference. Relative bioavailability of melatonin sustained release tablet to normal capsule was 83.8%, and absolute bioavailability was 3.75% for sustained release tablet and 4.49% for capsule. Conclusion The melatonin sustained release tablet was well formulated. The absolute bioavilability for oral administration of either sustained release tablet or unmodified release capsule of melatonin was less than 5%. The bioavailability of melatonin sustained release tablet was lower than that of unmodified release capsule, but MRT of sustained release tablet was significantly longer than that of capsule.

Tunable and sustained-release characteristics of venlafaxine hydrochloride from chitosan–carbomer matrix tablets based on in situ formed polyelectrolyte complex film coating

The objective of this study is to design sustained-release tablets using matrix technology, which can well control the release of highly water-soluble drugs with good system robustness and simple preparation process. Taking venlafaxine hydrochloride(VH) as a drug model, the feasibility of using chitosan(CS), carbomer(CBM) combination system to achieve this goal was studied. Formulation and process variables influencing drug release from CS–CBM matrix tablets were investigated. It was found that CS–CBM combination system weakened the potential influence of CS, CBM material properties and gastric emptying time on drug release profile. Demonstrated by direct observation, differential scanning calorimetry(DSC) and Fourier transform infrared spectroscopy(FTIR), in situ self-assembled polyelectrolyte complex(PEC) film was formed on the tablet surface during gastrointestinal tract transition, which contributed to the tunable and robust control of drug release. The sustained drug release behavior was further demonstrated in vivo in Beagle dogs, with level A in vitro and in vivo correlation(IVIVC) established successfully. In conclusion, CS–CBM matrix tablets are promising system to tune and control the release of highly water-soluble drugs with good system robustness.

HPLC Method for the Determination of Tamsulosin Hydrochloride in Sustained Release Tablets

The development and validation of an isocratic high performance liquid chromatographic method is described for the determination of tamsulosin hydrochloride in sustained release tablets. The determination was performed on a Diamonsil BDS C18 column with a mobile phase consisting of a mixture of acetonitrile, methanol and 0 5% phosphoric acid solution (20∶30∶50, V/V/V ) at a flow rate of 1 0 mL/min. UV detection was made at 274 nm. The linear range for tamsulosin hydrochloride was 0 81-8 10 μg/mL. The mean recovery was 99 8% ( S R=0 7%, n =9), and the precision was found to be 0 45% ( n =9). The proposed method can be used for routine analysis of tamsulosin hydrochloride in sustained release tablets.

Efficacy of Metoprolol Succinate Sustained Release Tablets Combined with Wenxin Granules in the Treatment of Coronary Heart Disease Arrhythmia

Objective:To explore the effect of metoprolol succinate sustained-release tablets combined with Wenxin Granules in the treatment of coronary heart disease patients with arrhythmia.Methods:The research objects were 50 patients with arrhythmia who were treated in our hospital from September 2019 to September 2020.According to different treatment methods,they were divided into observation group(Wenxin Granule+metoprolol succinate treatment)and control group(metoprolol succinate treatment),25 cases in each group.The curative effects of the two groups were compared.Results:After treatment,there was no significant difference in rnn50,RMSSD,sdnni and SDANN between the two groups(P>0.05).Compared with the control group,the SDNN in the observation group was higher than that in the control group(P<0.05);Before treatment,there was no significant difference in the above indexes between the two groups(P>0.05);The effective rates of the observation group and the control group were 92.00%and 68.00%respectively,and the curative effect of the observation group was higher than that of the control group(P<0.05);There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:In the treatment of patients with coronary heart disease and arrhythmia,Wenxin Granule Combined with metoprolol succinate sustained-release tablets has significant effect,which can effectively improve the dynamic electrocardiogram indexes of patients,improve the clinical efficacy,and has high safety.

Investigation of the potential application of sodium bentonite as an excipient in formulation of sustained release tablets

In this study, the application of sodium bentonite(SB) in formulation of tablets prepared by direct compression for oral administration was tested. Three different model drugs with different solubilities: paracetamol, diclofenac sodium and metformin HCl were tested. Each drug was mixed with SB at ratio of 50% and the mixtures were subsequently compressed.Compatibility studies were conducted using both Deferential Scanning Calorimeter(DSC)and Fourier Transform Infrared Spectroscopy(FTIR). The dissolution profile for each drug was determined in USP-buffers at different time intervals. Diclofenac sodium in pH 6.8 buffer and paracetamol in both pH 6.8 and pH 4.5 buffers showed extended release. However,metformin HCl showed immediate release at the different pH values. The study showed that using SB was possible to prepare tablets with different release profiles. However, these profiles differ depending on dissolution media and drug type.

Clinical Efficacy of Metoprolol Succinic Acid Sustained Release Tablets Combined with Trimetazidine in the Treatment of Gastrointestinal Tumors with Angina Pectoris

Objective:To investigate the clinical efficacy of metoprolol succinate sustained-release tablets combined with trimetazidine in the treatment of gastrointestinal tumors with angina pectoris.Methods:We enrolled the 58 patients with digestive tract tumor merger angina in November 2017-October 2019 and analysis the hospital clinical data by retrospective method.We included patients with routine treatment in control group(n=31 cases)and the subjects treated with increased dose of succinic acid metoprololzyban joint with trimetazidineinobservation group(n=27 cases)according to the different treatment group.Results:The effective rate of angina pectoris treatment in the observation group was higher than that in the control group.Furthermore,the incidence of adverse reactions was lower than that in the control group and the difference was statistically significant(P<0.05).Conclusion:Metoprolol succinic acid sustained release tablets combined with trimetazidine in the treatment of gastrointestinal tumors with angina pectoris can improve the efficacy of angina pectoris.The drug use is safe and worthy of clinical use.

Preparation for Polyvinyl Alcohol Hollow Microsphere and Its Sustained Release Effect on Urea

[Objective] The aim of this study was to discuss the optimizing preparation conditions of polyvinyl alcohol(PVA)hollow microsphere and its application in the production of slow-release urea fertilizer.[Method]PVA hollow microsphere was prepared by the emulsion chemical cross-linking method,while its composition,morphology and particle size was analyzed by technologies of FT-IR,SEM and TEM respectively.Thus,factors such as rate of emulsified speed,crosslink temperature and linking agent amount with effects on morphology and particle size of hollow microsphere were also discussed in this study.Furthermore,based on the optimizing preparation conditions,PVA fertilizer carrier microsphere was prepared by coating urea to investigate its sustained release effect on urea.[Result]The optimizing preparation conditions of polyvinyl alcohol(PVA)hollow microsphere were as follows:rate of emulsified speed 6 000 r/min,crosslink temperature 35 ℃ and linking agent amount 25 ml.PVA fertilizer carrier microsphere had significant sustained release effect on urea,and the optimal cross-linking time was 3 hours.[Conclusion]This study provides theoretical basis for the development of new slow-release fertilizer.

Pharmacokinetic Study on Lovastatin Sustained-release Tablet and Sustained-release Capsule in Begal Dogs

This study pharmacokinetically examined the lovastatin sustained-release tablet and sustained-release capsule in Beagle dogs. An reversed-phase HPLC method was established for the determination of lovastatin in Beagle dog plasma. Pharmacokinetic findings were compared among three preparation(lovastatin sustained-release tablet,T p; sustained-release capsule,T J and conventional capsule). Our results showed that the pharmacokinetic parameters in 6 dogs after single-dose oral administration of three perparations were calculated. T max, C max and MRT revealed significant difference (P<0.05). Relative bioavailability was 111.5±16.9 % (T P) and 110.4%±9.6 % (T J). The pharmacokinetic parameters in the 6 dogs after multiple-dose oral administration of three perparations, T max, C max MRT and DF had significant difference (P<0.05); C av , C min and AUC 0-24 h displayed no significant difference (P>0.05). It is concluded that the lovastatin sustained-release tablet and sustained-release capsule are able to maintain a sustained-release for 24 h.

Compound Metformin/Glipizide Bilayer Extended Release Tablets: Development and in Vitro Release

Aim In this study, compound metformin/glipizide bilayer extended release tablets were formulated with hydroxypropyl methylcellulose （HPMC） by wet granulation technique in order to tackle the problems associated with the muhidrug therapy of non-insulin dependent diabetes mellitus. Me^ls High-dose metformin is difficult to formulate into a tablet dosage form due to its poor compressibility and compactibility. In this study, the way to overcome the difficulty was to utilize stearic alcohol to prepare the tablet formulation. The influences of viscosity, amount of HPMC, and weight of fillers were investigated. The optimal formulation had acceptable physicochemical properties and released metformin and glipizide over 10 h. Results The data of metformin obtained from in vitro release fitted Higuchi kinetics best, while the release of glipizide in vitro was found to follow zero kinetics. Conclusion Compound metformin/glipizide bilayer extended release tablets have been successfully developed.

Influence of Preparation Factors on the Sustained Release of Nifedipine from Eudragit RL/RS Microspheres

Sustained release Eudragit RL/RS microspheres encapsulating nifedipine were prepared using the acetone/liquid paraffin emulsion solvent evaporation method. The influence of different preparation factors on release of the drug in vitro was investigated. The release rate of nifedipine from the microspheres increased with increasing Eudragit RL/RS ratio and stirring rate during the preparation, and with decreasing the polymer concentration of internal phase and microsphere size. It was found that a linear relationship existed between the microsphere size and the time of 50% drug release. The drug release rate increased with increasing nifedipine content from 4.2 to 16.7% and was more rapid than the dissolution rate of pure nifedipine particles. However, the release rate of the microspheres with 26.6% drug content decreased significantly and was slower than the dissolution rate of pure drug particles. This was attributed mainly to the nifedipine dispersion state in the microspheres as confirmed by the differential thermal analysis and X ray diffraction study, which showed that nifedipine was present in an amorphous or molecular state in the microspheres with 4.2, 9.4 and 16.7% drug, whereas partly in the crystalline state in the microspheres with 26.6% drug. The amounts released for less than 70% nifedipine can be fitted to Higuchi square root of time model, independent of polymer ratio, drug content and microsphere size.

Pharmacokinetics of Controlled Release and Immediate Release Morphine Sulphate Tablets after a Single Dose and Multiple Doses in Chinese Volunteers

The pharmacokinetics of morphine sulphate was studied in 10 Chinese healthy volunteers after a single oral dose. Blood samples were collected before and after administration of controlled release tablets (CRMS, 30 mg) and immediate release tablets (IRMS, 20 mg). The plasma concentration of morphine was determined by GC MS. The pharmacokinetic parameters of controlled release tablets and immediate release tablets were calculated∶ C max was 19.38±3.80 and 21.27±6.21 ng/ml, t max was 2.36 ±0.37 h and 0.56±0.16 h, t 1/2β was 3.53±0.87 and 3.03±0.74 h, AUC was 145.15±17.65 and 93.08±16.65 ng/ml, respectively. The steady state plasma concentration of morphine sulphate in cancer patients after multiple doses was achieved, C max of CRMS and IRMS was 27.43±0.33 ng/ml and 22.68±0.16 ng/ml, C min of CRMS and IRMS was 19.45±1.44 ng/ml and 18.14±0.49 ng/ml, respectively.

Evaluation of gum mastic(Pistacia lentiscus) as a microencapsulating and matrix forming material for sustained drug release

In this study, a natural gum mastic was evaluated as a microencapsulating and matrixforming material for sustained drug release. Mastic was characterized for its physicochemical properties. Microparticles were prepared by oil-in-oil solvent evaporation method. Matrix tablets were prepared by wet and melt granulation techniques. Diclofenac sodium(DFS) and diltiazem hydrochloride(DLTZ) were used as model drugs. Mastic produced discrete and spherical microspheres with DLTZ and microcapsules with DFS. Particle size and drug loading of microparticles was in the range of 22–62 μm and 50–87%, respectively. Increase in mastic:drug ratio increased microparticle size, improved drug loading and decreased the drug release rate. Microparticles with gum: drug ratio of 2:1 could sustain DLTZ release up to 12 h and released 57% DFS in 12 h. Mastic produced tablets with acceptable pharmacotechnical properties. A 30% w/w of mastic in tablet could sustain DLTZ release for 5 h from wet granulation,and DFS release for 8 h and 11 h from wet and melt granulation, respectively. Results revealed that a natural gum mastic can be used successfully to formulate matrix tablets and microparticles for sustained drug release.

Development of composite PLGA microspheres containing exenatide-encapsulated lecithin nanoparticles for sustained drug release

This study aimed to prepare poly(D, L-lactic-co-glycolic acid) microspheres(PLGA-Ms)by a modified solid-in-oil-in-water(S/O/W) multi-emulsion technique in order to achieve sustained release with reduced initial burst and maintain efficient drug concentration for a prolonged period of time. Composite PLGA microspheres containing exenatideencapsulated lecithin nanoparticles(Ex-NPs-PLGA-Ms) were obtained by initial fabrication of exenatide-loaded lecithin nanoparticles(Ex-NPs) via the alcohol injection method,followed by encapsulation of Ex-NPs into PLGA microspheres. Compared to Ms prepared by the conventional water-in-oil-in-water(W/O/W) technique(Ex-PLGA-Ms), Ex-NPs-PLGAMs showed a more uniform particle size distribution, reduced initial burst release, and sustained release for over 60 d in vitro. Cytotoxicity studies showed that Ms prepared by both techniques had superior biocompatibility without causing any detectable cytotoxicity.In pharmacokinetic studies, the effective drug concentration was maintained for over 30 d following a single subcutaneous injection of two types of Ms formulation in rats, potentially prolonging the therapeutic action of Ex. In addition, administration of Ex-NPs-PLGA-Ms resulted in a more smooth plasma concentration-time profile with a higher area under the curve(AUC) compared to that of Ex-PLGA-Ms. Overall, Ex-NPs-PLGA-Ms prepared by the novel S/O/W method could be a promising sustained drug release system with reduced initial burst release and prolonged therapeutic efficacy.

Light-induced ZnO/Ag/rGO bactericidal photocatalyst with synergistic effect of sustained release of silver ions and enhanced reactive oxygen species

Silver nanoparticles (Ag NPs) can effectively address the issue of antibiotic-resistant bacterial infections to reduce the potential toxicity of Ag NPs. Although challenging, it is, therefore, necessary to achieve the sustainable release of Ag+ ions from a finite amount of Ag NPs. This study aims at designing an efficient and benign antimicrobial silver-based ternary composite composed of photocatalysis zinc oxide (ZnO) and reduced graphene oxide (rGO) as a carrier, in which the reactive oxygen species (ROS) excited from ZnO and Ag+ ions released from the Ag NPs cooperate to realize an effective antibacterial activity against E. coli and S. aureus. The constant effective bacterial performance of the ternary photocatalyst with minimum Ag content can be attributed to the increase in the available quantity of ROS, which results from the enhanced separation efficiency of the photogenerated carriers. The proposed system notably realized the long-term sustainable release of Ag+ ions with low concentration for 30 days when compared with an equivalent amount of silver nitrate. Moreover, the use of the composite prevents biotoxicity and silver wastage, and imparts enhanced stability to the long-lasting antibacterial efficacy.

Sustained release donepezil loaded PLGA microspheres for injection:Preparation,in vitro and in vivo study

The purpose of this study was to develop a PLGA microspheres-based donepezil(DP)formulation which was expected to sustain release of DP for one week with high encapsulation efficiency(EE).DP derived from donepezil hydrochloride was encapsulated in PLGA microspheres by the O/W emulsion-solvent evaporation method.The optimized formulation which avoided the crushing of microspheres during the preparation process was characterized in terms of particle size,morphology,drug loading and EE,physical state of DP in the matrix and in vitro and in vivo release behavior.DP microspheres were prepared successfully with average diameter of 30m,drug loading of 15.92±0.31%and EE up to 78.79±2.56%.Scanning electron microscope image showed it has integrated spherical shape with no drug crystal and porous on its surface.Differential scanning calorimetry and X-ray diffraction results suggested DP was in amorphous state or molecularly dispersed in microspheres.The Tg of PLGA was increased with the addition of DP.The release profile in vitro was characterized with slow but continuous release that lasted for about one week and fitted well with first-order model,which suggested the diffusion governing release mechanism.After single-dose administration of DP microspheres via subcutaneous injection in rats,the plasma concentration of DP reached peak concentration at 0.50 d,and then declined gradually,but was still detectable at 15 d.A good correlation between in vitro and in vivo data was obtained.The results suggest the potential use of DP microspheres for treatment of Alzheimer’s disease over long periods.

Tablets of paliperidone using compression-coated technology for controlled ascending release

The aim of this work was to prepare ascending release compression-coated(CC) tablets with paliperidone(PAL) using a simple manufacturing technique and short manufacturing process.The release behavior and mechanisms in vitro of the final tablets was investigated and evaluated. The PAL CC tablets were comprised of a core layer of high viscosity hydroxypropyl cellulose(HPC-H) and a coating layer of high viscosity hydroxypropyl methylcellulose(HPMCK100 M). Several factors such as materials and core tablet compositions were studied for their influence in the formulation procedure. The drug release mechanism was studied using gravimetric analysis. The data could be fitted to the Peppas model. The ascending drug release results were expressed in terms of the slope of the release curve at different time points.Results showed that the formulation could achieve a good ascending drug release when the weight ratio of PAL was 5:1(core:layer). The fraction of HPC and HPMC was 33 %, and the combination of Eudragit RL-PO was 10%. The ascending release mechanism was due to solvent penetration into the PAL CC tablets, and subsequent drug dissolution from the gelatinous HPC and HPMC matrix erosion. The release mechanism was therefore a combination of diffusion and erosion. This work demonstrated that the compression-coated tablets could achieve controlled ascending release over 24 h for the oral administration systems.