Efficacy, Safety, and Retention Rate of Extended-Release Divalproex Versus Conventional Delayed-Release Divalproex: A Meta-Analysis of Controlled Clinical Trials.

Purpose: A novel once-daily divalproex-extended release (ER) dose formulation has been developed; this formulation prolongs the therapeutic serum levels of the drug, compared with the twice-daily conventional divalproex-delayed release (DR) formulation. This study aimed to systematically examine and compare the efficacy, safety, and retention rates of the ER divalproex (VPA-ER) and conventional DR divalproex (VPA-DR) formulations. Methods: Randomized control trials (RCTs) reporting the efficacy, adverse events (AEs), and medication compliance of ER and DR divalproex were searched in online databases, including PubMed, Embase, and Cochrane Library databases, by searching MeSH words and term words. Observational studies with potential biases were excluded. The meta-analysis was performed using Stata 16.0 software. Findings: Thirteen RCTs, involving 1,028 participants, were included in this meta-analysis. Efficacy, AEs, and drug retention rates were the main study outcomes. According to our study, VPA-ER presented clinically significant benefits compared with the placebo in the population with bipolar disorder (BD) (39.5% versus 27.2%, p < 0.001). A similar efficacy of VPA-ER and VPA-DR in controlling seizures was observed in epilepsy patients (87.4% versus 86.5%, p = 0.769). A significantly lower incidence of AEs was reported in the VPA-ER group than in the placebo group (26.8% versus 34.8%, p = 0.003). By contrast, there was no evidence of difference in safety between VPA-ER and VPA-DR (29.4% versus 30.5%, p = 0.750). In addition, the drug retention rate was significantly lower in the VPA-ER group than in the placebo group (76.0% versus 82.7%, p = 0.020), especially in migraine patients (p = 0.022) and in patients who were treated for fewer than 4 weeks (p = 0.018). Implications: The efficacy of VPA-ER was significantly superior to that of the placebo treatment, which provided efficacy similar to that of conventional VPA-DR. VPA-ER is well tolerated with a low rate of AEs compared to the placebo. In addition, the acceptable medicine compliance of VPA-ER was conducive to the long-term maintenance treatment of chronic diseases. Although we analyzed open labels and crossover design RCTs, large-scale multicenter studies on the efficacy and medicine compliance of new ER formulations with less AEs are required to validate our conclusion.

Effect of different physical activity training methods on epilepsy: A protocol for systematic review and meta-analysis.

BACKGROUND: Over the past few decades, people with epilepsy were advised not to engage in sports based on the fear that sporting activity may cause injuries, potentially induce seizures, and have a negative effect on disease course. However, in recent years, numerous studies have indicated a positive role of physical exercise in reducing the frequency of seizures and improving health condition of patients with epilepsy. The purpose of this study was to compare the effects of different physical exercise programs on the symptomatology and health condition of individuals with epilepsy and provide guidance for selecting the optimal modality of physical exercise for patients with epilepsy via a meta-analysis of available literature. METHODS: A literature search was carried out in MEDLINE via PubMed, Cochrane Library, EBSCO, Embase, China National Knowledge (CNKI), and Wan fang databases to gather relevant data about different physical exercise modalities and epilepsy. We will use Endnote X9 software for studies selection and Stata16.0 software for the data analysis. RESULTS: This present study aimed to provide the most up to date evidence and recommendations for clinicians and epilepsy patients to choose an optimal type of exercise. CONCLUSION: Aerobic exercise and resistance exercises both had a positive effect on epilepsy patients. Persons with epilepsy should be encouraged to participate in sports activities.INPLASY registration number: INPLASY202220070.

Material Attribute Research in Quality Control of Traditional Chinese Medicine Pills： A Review / 中国实验方剂学杂志

As intelligent production of traditional Chinese medicine （TCM） has been inevitable， informatization and automation of the production process have become the precondition for realizing intelligent manufacturing of TCM， of which the accumulation of critical material attribute and the critical quality attribute are the basis. The study of material properties is of great significance to achieve the quality control of the final product in the process， but there is a lack of systematic induction and summary of the research on the attribute of TCM pills. Therefore， the authors analyzed and summarized the attributes of raw materials， excipients and intermediates in the pill unit process according to the classification of powder properties， rheological properties and texture properties. What’s more， the impact of material attributes on the quality of the final product was summarized. Besides， this review summarized the attribute characterization techniques involved in the pill process and provided some suggestions for the characterization of product quality attributes. Finally， based on the concept of quality by design （QbD）， the authors proposed that the study of material attribute should be combined with process analytical technology （PAT）， and the focus of drug quality control should be moved forward to guide equipment upgrading， so as to realize intelligent continuous manufacturing of TCM pills.

Efficacy, safety, and retention rate of extended-release divalproex versus conventional delayed-release divalproex: A protocol for systematic review and meta-analysis.

BACKGROUND: A novel once-daily divalproex-extended release (VPA-ER) dose formulation has been developed, which prolongs therapeutic serum levels compared with that of twice-daily conventional divalproex-delayed release (VPA-DR). Currently, there is lack of meta-analysis focusing on drug retention rate between VPA-ER and VPA-DR. Thus, our study is the first one that aims to systematically examine and compare the efficacy, safety, and retention rate of VPA-ER and VPA-DR. METHODS: Online databases including MEDLINE via PubMed, Cochrane Library, Embase (up to October 30, 2021) will be applied for literature screen. We will conduct meta-analysis by using Stata16.0 software. RESULTS: This study aims to evaluate the efficacy, safety, and drug retention rate of VPA-ER versus conventional VPA-DR. CONCLUSION: Once-daily VPA-ER may present a positive efficacy and not increase the incidence of AEs and has a higher retention rate for patients, which can be used as a substitute for conventional VPA-DR.INPLASY registration number: INPLASY2021110090(DOI: 10.37766/inplasy2021.11.0090).

Effects of source difference of sodium carboxymethyl starch on its properties and function / 药学学报

During the process of consistency evaluation, it was found that the consistency of drug release between generic and original brands in vitro was not sufficient to demonstrate their same release in vivo. The disintegration of tablets, as a premise for the release of tablet drugs, greatly affects the release of drugs, depending on the structure and properties of disintegrants. Hence the systematic research on disintegrants would be very important for the evaluation of generic consistency. In this experiment, the physicochemical properties and application of 11 different sodium carboxymethyl starch (CMS-Na) from 9 manufacturers were investigated. This provides the reference for selection of excipients for consistency evaluation. The particle morphology of CMS-Na was observed by scanning electron microscope. The particle size distribution was determined by dry particle size analyzer. The determination of pH and loss on drying was carried out according to the 2015 edition of Chinese pharmacopoeia method. The powder fluidity was evaluated with Carr's index, Hausner ratio and angle of repose. The disintegration performance of CMS-Na was evaluated through determining the water absorption and swelling. The disintegration effect of CMS-Na tablets was studied using lactose and microcrystalline cellulose as fillers. The results showed that pH values and weight loss on drying of all samples met the requirements, whereas the particle morphology, fluidity, water swell-ability and disintegration time had a large variation, which leads to the large differences the properties of CMS-Na depending on the sources. Therefore in order to ensure that the reproducibility of generic drugs from their name brand, our studies indicate that only a sizable choice of disintegrants could ensure good inter batch reproducibility.

Solubilization and protection of curcumin by mixed surfactants / 药学学报

The solubilization and protection of curcumin (Cur) by mixed surfactants were studied through the determination about the critical micellar concentration (CMC) of the mixed surfactants of Tween 80 and dodecyl trimethyl ammonium bromide (DTAB), molar solubilization ratio (MSR), degradation rate (k) of Cur in pH 13 solution and mixed surfactant solutions prepared at pH 13. The results showed that when Tween 80 was used alone, it exhibited high solubilization ability but poor stability. DTAB was used alone, it showed strong stability but poor solubilization ability. When DTAB was mixed with Tween 80 at different mole fractions, the stability of Cur was enhanced, and the best stability was observed when the mole fraction of DTAB was 0.4, although the solubilization ability was not the best at this mole fraction, but MSR was increased by 1.7 times compared to DTAB used alone. Mixed surfactant not only increased the solubility but also improved the stability of Cur. In addition, mixed surfactant has the advantages of less dosage and low toxicity, which is worth popularizing in application.

Rheological properties of compound carrageenan / 药学学报

The rheological properties of six compound gels that consists of kappa carrageenan (KC) and another excipient such as konjac gum were explored through comparison of their viscosity measured by the rotation method. The gel fluid type was dependent on the rheological curve fitted by the power-law equation. The effect of concentration on the viscosity of different compound gels was investigated by establishing the linear equation between their viscosity and concentration, the slope of which was used to determine the relation between viscosity and concentration of different compound gels. The viscous flow activation energy (Eη) was calculated by the Arrhenius equation, which was able to investigate the effect of temperature on their viscosity. The interaction between monomer and compound gels was also studied by measuring their viscosity. The results showed that six compound gels were pseudoplastic fluid. Among all compound gels, the KC-xanthan gum (KC-XG) solution exhibited the most obvious shear thinning, the strongest pseudoplasticity, while the smallest Eη, resulting in the best thermal stability of viscosity. Furthermore, the concentration of KC-sodium hyaluronate (KC-HA-Na) solution affected its viscosity significantly. The viscosity of six compound gels was greater than the summation of the two kinds of monomer gels, which suggests that there is a synergistic-viscosity interaction between KC and another excipient.

Determination of contact angle of pharmaceutical excipients and regulating effect of surfactants on their wettability / 药学学报

To study the effects of surfactants on wettability of excipients, the contact angles of six types of surfactants on the surface of two common excipients and mixture of three surfactants with excipients were measured using hypsometry method. The results demonstrated that contact angle of water on the surface of excipients was associated with hydrophilcity of excipients. Contact angle was lowered with increase in hydrophilic groups of excipient molecules. The sequence of contact angle from small to large was starch < sodium benzoate < polyvinylpyrrolidone < sodium carboxymethylcellulose < sodium alginate < chitosan < hydroxypropyl methyl cellulose <magnesium stearate. In addition, surfactants both in droplets and mixed in excipients significantly reduced the contact angle of excipients, and their abilities to lower contact angle varied. The results of the present study offer a guideline in the formulation design of tablets.