Upadacitinib sustained-release tablets for the treatment of chronic refractory gouty arthritis: a case report and literature review.

Background: Gouty arthritis (GA) is a crystal-related joint disease caused by the deposition of monosodium urate (MSU) crystals, directly associated with hyperuricemia resulting from purine metabolism disorder and/or reduced uric acid excretion. Acute attacks of typical gouty arthritis are generally relieved through the clinical use of NSAIDs, colchicine, or glucocorticoids. However, managing patients with chronic refractory gout poses challenges due to complications such as multiple tophi, gouty nephropathy, diabetes, and gastrointestinal bleeding. While there have been numerous studies on gout in recent years, research specifically regarding chronic refractory gout remains limited. The management of such cases still faces several unresolved issues, including recurrent disease flare-ups and poor patient compliance leading to inadequate drug utilization and increased risk of side effects. In this report, we present a case of successful improvement in chronic refractory gouty arthritis using the biologic agent upadacitinib sustained-release tablets. Case presentation: Our case report involves a 53 years-old Asian patient with recurrent gouty arthritis who had a history of over 20 years without regular treatment, presenting with tophi and an increasing number of painful episodes. During hospitalization, various analgesics and anti-inflammatory drugs provided inadequate relief, requiring the use of steroids to alleviate symptoms. However, tapering off steroids proved challenging. We decided to add upadacitinib sustained-release tablets to the treatment regimen, which ultimately improved the patient's condition. After 6 months of follow-up, the patient has not experienced any further acute pain episodes. Conclusion: This case highlights the potential therapeutic effect of upadacitinib sustained-release tablets during the acute phase of chronic refractory gouty arthritis.

Clinical Efficacy of Fuzheng Huaji Longbi Decoction in Treating Benign Prostatic Hyperplasia with Syndrome of Healthy Qi Deficiency and Blood Stasis / 中国实验方剂学杂志

ObjectiveTo explore the clinical efficacy and safety of Fuzheng Huaji Longbi decoction in treating benign prostatic hyperplasia （BPH） in the patients with the syndrome of healthy Qi deficiency and blood stasis. MethodA total of 94 BPH patients were randomized into control and observation groups， with 47 patients in each group. The control group was treated with doxazosin mesylate sustained-release tablets， and the observation group with Fuzheng Huaji Longbi decoction on the basis of the therapy in the control group. After eight weeks， the international prostate symptom score （IPSS）， quality of life （QOL） score， residual urine volume （RUV）， maximum urinary flow rate （Qmax）， TCM syndrome score， TCM symptom score， electrocardiogram， and liver and kidney function were determined to evaluate the clinical efficacy and safety of the two groups. ResultAfter 8 weeks of treatment， the total response rate in the control group was 63.64% （28/44）， which was lower than that （84.44%， 38/45） in the observation group （χ2=5.026， P<0.05）. The clinical efficacy in the observation group was higher than that in the control group （Z=-2.17， P=0.030）. The treatment in both groups decreased the IPSS， QOL score， RUV， and TCM syndrome scores and increased the Qmax （P<0.05）. Moreover， the observation group had lower IPSS， QOL score， RUV， and TCM syndrome score （P<0.05） and higher Qmax than the control group after treatment （P<0.05）. The treatment in the observation group decreased all the TCM symptom scores （P<0.05）， while that in the control group only decreased the frequency of urination at night and the scores of dysuria， weak urine stream， and post-urinary drainage （P<0.05）. After treatment， the observation group had lower frequency of urination at night and lower scores of mental fatigue， cold limbs， lower abdominal discomfort， and loose stool than the control group （P<0.05）. No adverse events associated with the administration of Fuzheng Huaji Longbi decoction were observed during the treatment period. ConclusionFuzheng Huaji Longbi decoction is effective in treating BPH in the patients with the syndrome of healthy qi deficiency and blood stasis. It can relieve the clinical symptoms and improve the quality of life， being a safe and reliable choice for clinical application.

Development and Validation a UPLC-MS/MS Method for Quantification of Pentoxifylline in Beagle Plasma: Application for Pharmacokinetic Study of Food Effect.

Purpose: To develop an UPLC-MS/MS method for the quantitative analysis of pentoxifylline in beagle dog plasma and apply it to a pharmacokinetic study of food effect. Methods: Sample separation was achieved using a Kinetex Phenyl-Hexyl column (50 × 2.1 mm, 1.7 µm) with a gradient elution program in 5.5 min after a simple protein precipitation with methanol. Using the mobile phase that made up by 0.2% formic acid and 5mM ammonium formate water (A) and methanol (B). Quantitation was carried out using the positive ionization mode with multiple reaction monitoring (MRM). A randomized, single-dose, two-period crossover study was conducted in six fasted or fed beagles that received 400 mg pentoxifylline sustained-release tablets (Brand name: Shuanling™, CSPC Pharmaceutical Group). WinNonlin® software was used to calculate pharmacokinetic parameters. Results: The linear calibration range was 2-1000 ng/mL (r2> 0.99). Both intra- and inter-batch precision were less than 6.27%, and the accuracy ranged from 88.65% to 97.18%. Pentoxifylline was readily absorbed in fasted and fed dogs administered a dose of 400 mg (tmax:1.54h vs 1.83h). Compared to the fasted group, the AUC0→t and Cmax in the fed group increased by 1.71-fold and 1.30-fold, respectively. In the fasted group, the AUC0→t and Cmax values were 4684.08 h•ng/mL and 2402.33 ng/mL, respectively. In the fed group, these values were 8027.75 h•ng/mL and 3119.67 ng/mL. The difference in AUC0-t between the fed and fasted group was statistically significant. Conclusion: The novel optimized UPLC-MS/MS assay is an effective tool for the determination of pentoxifylline and has been successfully applied in pharmacokinetic studies of pentoxifylline in beagle dogs. The administration of pentoxifylline sustained-release tablets with food significantly increased the area under the time curve, and it is recommended that they should be administered during or shortly after feeding.

Convolutional neural network-based evaluation of chemical maps obtained by fast Raman imaging for prediction of tablet dissolution profiles.

In this work, the capabilities of a state-of-the-art fast Raman imaging apparatus are exploited to gain information about the concentration and particle size of hydroxypropyl methylcellulose (HPMC) in sustained release tablets. The extracted information is utilized to predict the in vitro dissolution profile of the tablets. For the first time, convolutional neural networks (CNNs) are used for the processing of the chemical images of HPMC distribution and to directly predict the dissolution profile based on the image. This new method is compared to wavelet analysis, which gives a quantification of the texture of HPMC distribution, carrying information regarding both concentration and particle size. A total of 112 training and 32 validation tablets were used, when a CNN was used to characterize the particle size of HPMC, the dissolution profile of the validation tablets was predicted with an average f2 similarity value of 62.95. Direct prediction based on the image had an f2 value of 54.2, this demonstrates that the CNN is capable of recognizing the patterns in the data on its own. The presented methods can facilitate a better understanding of the manufacturing processes, as detailed information becomes available with fast measurements.

Bioequivalence of metformin hydrochloride sustained-release tablets under fed condition in healthy subjects / 中国药科大学学报

@#To evaluate bioequivalence and safety of two kinds of metformin hydrochloride sustained-release tablets (test preparation vs reference preparation) under the condition of fed and single administration.A single center, randomized, open, single-dose, two-period, two-sequence, and double-crossover design was used.32 healthy subjects took 0.5 g of test preparation or reference preparation under fed and single-dose administration.4 mL of venous blood was collected from before administration (0 h) to 1, 3, 4, 4.5, 5, 5.5, 6, 7, 8, 9, 10, 12, 15, 24, 36 and 48 h after administration.The concentration of metformin in plasma samples was detected, and then the pharmacokinetic parameters were calculated by WinNonlin 7.0 software.When the 90% confidence intervals of cmax, AUC0-t and AUC0-∞ geometric mean ratio of test preparation and reference preparation were within 80.00%-125.00% equivalent intervals respectively, the bioequivalence of the two preparations was proved.One subject fell off due to adverse events.The main pharmacokinetic parameters of test preparation and reference preparation as follows: cmax were (0.68 ± 0.14) and (0.65 ± 0.11) mg/L, AUC0-t were (7.33 ± 1.65) and (7.00 ± 1.89) h·mg/L, AUC0-∞ were (7.39 ± 1.67) and (7.06 ± 1.91) h·mg/L, respectively.The 90% confidence intervals of the geometric mean ratio of the two main pharmacokinetic parameters were 101.45%-109.14%, 100.08%-112.32% and 100.24%-112.28%, respectively, which fell within the bioequivalence interval of 80.00%-125.00%.There were no serious adverse events and unexpected adverse events during the trial.The results show that test preparation and reference preparation are bioequivalent under fed and single-dose administration, safe and well tolerated in healthy subjects.

Investigation on the Potential Application of Na-Attapulgite as an Excipient in Domperidone Sustained-Release Tablets.

In this study, Na-attapulgite was explored as an excipient to prepare domperidone sustained-release tablets and test them in accordance with United States Pharmacopoeia requirements. Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) were employed to explore the compatibility between Na-attapulgite and domperidone. The XRD and DSC show no interaction between the drug and Na-attapulgite. The FTIR spectrum indicates a shift in the absorption of N-H in the drug molecule, which can be explained by the hydrogen bonding interaction between the N-H in the DOM molecule and the -OH on the surface of Na-ATP. The diameter, hardness, friability and drug content of the tablets were measured, and they all met the relevant requirements of the United States Pharmacopoeia. In addition, the tablets with Na-attapulgite as excipient exhibit a better release performance within the release time of 12 h. These results demonstrate that the domperidone sustained-release tablets have been successfully prepared by using Na-attapulgite as an excipient. The doping of Na-ATP in domperidone sustained-release tablets improves the cytocompatibility. Moreover, with the increase of Na-ATP content, cells proliferate remarkably and cell activity is significantly enhanced.

Dissolution profiles prediction of sinomenine hydrochloride sustained-release tablets using Raman mapping technique.

The work aims to explore the feasibility of Raman mapping in predicting the dissolution profiles of solid oral dosage form. In this study, N = 36 batches of representative sinomenine hydrochloride sustained-release tablets were prepared, using a D-optimal design, to introduce adequate variability, and the Raman mapping data of each tablet were acquired. The partial least squares regression models were established using three kinds of different modes, named single point mode, average mode and multi-point mode, to predict the dissolution profiles based on Raman mapping data. The percent dissolutions at specific time points and the parameters of an exponential function, which was employed to fit the dissolution profiles, were predicted, and the accuracy and precision of prediction were tested. The results showed that the multi-point mode displayed the best accuracy and precision in the prediction of both the dissolutions at the specific time points and the function parameters. In summary, the established method based on Raman mapping avoids the shortcomings of traditional dissolution testing protocols, such as complex operation, time-consuming and high analysis cost, thus has great potential of application and popularization.

Raman mapping-based non-destructive dissolution prediction of sustained-release tablets.

In this paper, the applicability of Raman chemical imaging for the non-destructive prediction of the in vitro dissolution profile of sustained-release tablets is demonstrated for the first time. Raman chemical maps contain a plethora of information about the spatial distribution and the particle size of the components, compression force and even polymorphism. With proper data analysis techniques, this can be converted into simple numerical information which can be used as input in a machine learning model. In our work, sustained-release tablets using hydroxypropyl methylcellulose (HPMC) as matrix polymer are prepared, the concentration and particle size of this component varied between samples. Chemical maps of HPMC are converted into histograms with two different methods, an approach based on discretizing concentration values and a wavelet analysis technique. These histograms are then subjected to Principal Component Analysis, the score value of the first two principal components was found to represent HPMC content and particle size. These values are used as input in Artificial Neural Networks which are trained to predict the dissolution profile of the tablets. As a result, accurate predictions were obtained for the test tablets (the average f2 similarity value is higher than 59 with both methods). The presented methodology lays the foundations of the analysis of far more extensive datasets acquired with the emerging fast Raman imaging technology.

Efficacy of maintenance electroconvulsive therapy combined with quetiapine treatment for manic episode of bipolar disorder / 中国基层医药

Objective:To investigate the efficacy of maintenance electroconvulsive therapy (MECT) combined with quetiapine treatment for manic episodes of bipolar disorder.Methods:A total of 103 patients with manic episodes of bipolar disorder received treatment in Kangci Hospital of Jiaxing from January 2019 to August 2020 and were included in this study. They were randomly divided into observation ( n = 46) and control groups ( n = 57). The observation group was given MECT combined with quetiapine treatment and the control group was treated with magnesium valproate sustained-release tablets combined with quetiapine. All patients received 4 weeks of treatment. Clinical efficacy, total hospital cost, drug cost during hospitalization, drug proportion, adverse reactions, and scores of the Bech-Rafaelsdn Mania Rating Scale and the Wisconsin Card Sorting Test pre- and post-treatment were compared between the two groups. Results:After 4 weeks of treatment, total response rate was significantly higher in the observation group than in the control group [76.09% (35/46) vs. 56.14% (32/57), χ2 = 4.45, P < 0.05]. In the observation group, total hospital cost, drug cost during hospitalization, and drug proportion were (16074.52 ± 1019.81) yuan, (1374.52 ± 619.81) yuan, and 8.70% respectively, which were not significantly different from those in the control group [(15618.14 ± 1550.34) yuan, (1261.14 ± 750.34) yuan, 10.53%, t = 1.71, 0.82, χ2 = 0.09, all P > 0.05]. After 4 weeks of treatment, Bech-Rafaelsdn Mania Rating score was significantly lower in the observation group than in the control group [(7.36 ± 3.04) points vs. (10.23 ± 2.37) points, t = 5.38, P < 0.001]. The number of wrong responses and the number of perseverative errors in the Wisconsin Card Sorting Test in the observation group were (40.45 ± 3.61) counts and (9.56 ± 1.39) counts, respectively, which were significantly lower than those in the control group [(48.59 ± 4.51) counts, (12.08 ± 1.25) counts, t = 10.17, 9.56, both P < 0.001]. The number of perseverative errors in the Wisconsin Card Sorting Test was significantly higher in the observation group than in the control group [(33.85 ± 2.50) counts vs. (29.71 ± 2.14) counts, t = 8.90, P < 0.001]. There was no significant difference in total incidence of adverse reactions between observation and control groups (21.74% vs. 22.81%, χ2 = 0.01, P > 0.05). Conclusion:MECT combined with quetiapine treatment is highly effective on the manic episodes of bipolar disorder. The combined therapy is worthy of clinical application.

Development and Bio-Predictive Evaluation of Biopharmaceutical Properties of Sustained-Release Tablets with a Novel GPR40 Agonist for a First-in-Human Clinical Trial.

Sustained-release (SR) formulations may appear advantageous in first-in-human (FIH) study of innovative medicines. The newly developed SR matrix tablets require prolonged maintenance of API concentration in plasma and should be reliably assessed for the risk of uncontrolled release of the drug. In the present study, we describe the development of a robust SR matrix tablet with a novel G-protein-coupled receptor 40 (GPR40) agonist for first-in-human studies and introduce a general workflow for the successful development of SR formulations for innovative APIs. The hydrophilic matrix tablets containing the labeled API dose of 5, 30, or 120 mg were evaluated with several methods: standard USP II dissolution, bio-predictive dissolution tests, and the texture and matrix formation analysis. The standard dissolution tests allowed preselection of the prototypes with the targeted dissolution rate, while the subsequent studies in physiologically relevant conditions revealed unwanted and potentially harmful effects, such as dose dumping under an increased mechanical agitation. The developed formulations were exceptionally robust toward the mechanical and physicochemical conditions of the bio-predictive tests and assured a comparable drug delivery rate regardless of the prandial state and dose labeled. In conclusion, the introduced development strategy, when implemented into the development cycle of SR formulations with innovative APIs, may allow not only to reduce the risk of formulation-related failure of phase I clinical trial but also effectively and timely provide safe and reliable medicines for patients in the trial and their further therapy.

Real-time release testing of dissolution based on surrogate models developed by machine learning algorithms using NIR spectra, compression force and particle size distribution as input data.

In this work spectroscopic measurements, process data and Critical Material Attributes (CMAs) are used to predict the in vitro dissolution profile of sustained-release tablets with three machine learning methods, Artificial Neural Networks (ANN), Support Vector Machines (SVM) and Ensemble of Regression Trees (ERT). Beside the effect of matrix polymer content and compression force, the influence of active pharmaceutical ingredient (API) and matrix polymer particle size distribution (PSD) on the drug release rate of sustained tablets is studied. The matrix polymer PSD was found to be a significant factor, thus this factor was included in the dissolution prediction experiments. In order to evaluate the importance of the inclusion of PSD data, models without PSD data were also prepared and the results were compared. In the developed models, the API and hydroxypropyl-methylcellulose (HPMC) content is predicted from near-infrared (NIR) spectra, the compression force is measured by the tablet press and HPMC particle size is measured off-line. The predictions of ANN, SVM and ERT were compared to the measured dissolution profiles of the validation tablets, ANN yielded the most accurate results. In the presented work, data provided by Process Analytical Technology (PAT) sensors is combined with CMAs for the first time to realize the Real-Time Release Testing (RTRT) of tablet dissolution.

Influencing factors of end-of-dose failure in patients with cancer pain after oral oxycodone sustained-release tablets: a retrospective, case-control study.

OBJECTIVE: Comparing the characteristics of end-of-dose failure patients and non-end-of-dose failure patients in the Chinese population and exploring the factors that may affect the occurrence of end-of-dose failure in cancer pain patients. METHODS: The outpatient with cancer pain from 2016 to 2019 were collected through hospital information system, and patients were included who met the following criteria: patients with the average numerical rating scale  ≥4 points within 3 days after taking the oxycodone sustained-release preparation, titrated to an effective therapeutic dose suitable for patients, had at least two clinical visits information of the patient with a minimum of ≥3 days between visits, the average numerical rating scale of the next visit after the treatment of occasional pain is ≥4, and were divided into end-of-dose failure group and non-end-of-dose failure group. RESULTS: Age (P < 0.05, odds ratio 0.933), diagnosis of nasopharyngeal carcinoma (P < 0.05, odds ratio 0.009), pain site is the head and neck (P < 0.05, odds ratio 0.005) and the abdomen (P < 0.01, odds ratio 0.021), and the metastatic site is the liver (P < 0.05, odds ratio 0.001) are related to the occurrence of end-of-dose failure. CONCLUSIONS: Younger patients are more likely to develop end-of-dose failure. Patients diagnosed with nasopharyngeal cancer, with pain in the head and neck and abdomen, and with liver metastases have a lower incidence of end-of-dose failure.

A 12-hour rapid titration method for cancer pain: a randomized, controlled, open-label study.

BACKGROUND: Opioid titration is the best way to achieve a balance of pain relief and tolerable side effects for moderate-to-severe cancer pain. Rapid dose titration helps to achieve early analgesia. We explored the efficacy and safety of a 12-hour rapid dose titration in treating cancer pain. METHODS: Opioid-naïve patients with moderate-to-severe cancer pain were randomly divided into oxycodone group and morphine group. The medicines were adjusted to oxycodone sustained-release tablets after 12 hours, and the dose of oxycodone sustained-release tablets was adjusted every 12 hours. The analgesic efficacy and adverse reactions during the treatment were observed until the 72nd hour. RESULTS: A total of 106 patients were included in the analysis, with 51 patients in the oxycodone group and 55 in the morphine group. The pain control rate of all patients reached 96.2% 24 hours after treatment, and it was not significantly different between two groups (P=0.619). The proportion of Numeric Rating Scale (NRS) score that decreased by ≥50% was significantly higher in the oxycodone group than in the morphine group (P=0.013). In the first 12 hours and 24 hours, significantly lower proportions of patients in the oxycodone group experienced multiple episodes of breakthrough pain (BTP) than in the morphine group (P=0.032, P=0.021, respectively). The quality of life of the patients in the oxycodone group was significantly higher than that in the morphine group at the 24th hour (P=0.047), as was the degree to which the quality of life had improved (P<0.001). Only grade 1 or 2 adverse reactions were observed during the study period, and no significant difference between two groups. CONCLUSIONS: The 12-hour rapid dose titration method can achieve early analgesia, with mild adverse reactions. In particular, the rapid titration method with background sustained-release oxycodone can reduce BTP episodes and achieve significant early pain relief.

In vitro and in vivo evaluation of a sustained-release once-a-day formulation of the novel antihypertensive drug MT-1207.

Hypertension is one of the most common chronic cardiovascular disorders. Sustained-release formulations are developed to maintain drug therapeutic levels throughout the treatment of hypertension, to promote patient compliance and improve patient outcomes. We have developed and tested in in vivo trials a once-a-day tablet formulation for the novel antihypertensive drug MT-1207. The tablets based upon a hydrophilic polymer matrix underwent post-compression parameter and physicochemical characterisations, along with in vitro drug release testing. The most promising formulation containing 31% w/w HPMC K15M gave a 24-hour release of MT-1207 with an almost constant release rate up to 20 hours. Follow in in vivo studies were carried out in Beagle dogs for the optimised sustained-release tablets in comparison to immediate-release tablets. The results showed that a sustained release of MT-1207 from the new formulation was achieved with a drug t1/2 2-2.5 times longer than the immediate-release tablets. Moreover, the AUC0-24h values of both sustained- and immediate-release tablets were identical at the same dose of 30 mg, indicating that the same amount of drug was absorbed in each case. For treatments based upon MT-1207, this development is significant for future commercial exploitation via scale-up and further trials, and for improved patient outcomes.

Bioequivalence of metformin hydrochloride sustained-release tablets in healthy subjects / 中国临床药理学与治疗学

AIM: To study the bioequivalence of two metformin hydrochloride sustained-release tablets in Chinese healthy subjects. METHODS: A randomized, open-label, two-period, crossover study design was adopted in the study. In fasting test 36 and in fed test 23 healthy subjects were given a single oral dose of metformin hydrochloride sustained-release tablet (0.5 g). The concentration of metformin in plasma was measured by HPLC-MS/MS. The pharmacokinetic parameters were calculated by WinNonlin 7.0 program, and statistical analysis were performed by using SAS9.4 statistics software. RESULTS: In the fasting test, the pharmacokinetic parameters of metformin of the test (T) and reference(R) preparation were as follow: C

In vitro evaluation of saxagliptin and metformin hydrochloride sustained-release tablets / 中国药科大学学报

@#In order to evaluate the consistency of the release behavior between the self-made saxagliptin and metformin hydrochloride sustained-release tablets and the reference preparations in vitro, the similarity of the dissolution curves between the self-made preparations and the reference preparations in four dissolution mediums: HCl (pH 1.0), acetate buffer saline (pH 4.5), phosphate buffer saline (pH 6.8) and pure water, and the gel morphology and strength of the self-made preparations and the reference preparations in the HCl (pH 1.0) solution medium were compared.Results showed that in four dissolution mediums, the dissolution rates of saxagliptin in the self-made preparations and the reference preparations at 15 min were greater than 85%, and the ?2 similarity factors of metformin hydrochloride were 89, 83, 80, 86, all greater than 50, so the dissolution of the self-made preparations was consistent with those of the reference preparations.The volume expansion rate, water absorption rate and erosion rate were consistent with those of the reference preparations, and the gel strength of the self-made preparations was the same as that of the reference preparations.The in vitro release behaviors of the self-made preparations and the reference preparations are consistent, which provide a good guarantee for bioequivalence.

Cost-effectiveness analysis of combining traditional Chinese medicine in the treatment of hypertension: compound Apocynum tablets combined with Nifedipine sustained-release tablets vs Nifedipine sustained-release tablets alone.

BACKGROUND: We evaluated the long-term cost-effectiveness of antihypertensive traditional Chinese medicines (TCMs) and to compare the cost-effectiveness of a combined treatment consisting of compound Apocynum tablets and Nifedipine sustained-release tablets with the cost-effectiveness of treatment with Nifedipine sustained-release tablets alone. METHODS: A Markov model was used to simulate the potential incremental cost-effectiveness per quality-adjusted life year (QALY) to be gained from compound Apocynum tablets and Nifedipine sustained-release tablets compared with Nifedipine sustained-release tablets alone. Model parameter estimates were informed by previously published studies. The direct medical costs of outpatients with hypertension were estimated from the health care provider's perspective. A 5% annual discount rate was applied to both costs and QALYs. RESULTS: TCMs combined with Nifedipine sustained-release tablets group generated a total 20-year cost of 11,517.94 RMB (US $1739.87), whereas Nifedipine sustained-release tablets alone group resulted in a 20-year cost of 7253.71 RMB (US $1095.73). TCMs combined with Nifedipine sustained-release tablets group resulted in a generation of 12.69 QALYs, whereas Nifedipine sustained-release tablets alone group resulted in 12.50. The incremental cost-utility ratio was 22,443.32 RMB (US $3390.23) per QALY. Considering the threshold of 1 GDP per capita in China in 2018 (US $9764.95), the combination of compound Apocynum tablets and Nifedipine sustained-release tablets was a cost-effective strategy. One-way and probabilistic sensitivity analysis showed unchanged results over an acceptable range. CONCLUSIONS: Combining Traditional Chinese Medicines with chemical medicines is more cost-effective strategy in the treatment of hypertension.

Subdivision of modified-release tablets: state-of-the-art and future perspectives.

Tablet splitting is a practice disseminated among health professionals for dose adjustments, swallowing facilitation or even treatment cost reduction. Nevertheless, tablets not designed for this purpose cause imprecise dosage and stability loss with important therapeutic repercussions. Novel technologies of modified drug release tablets have come to market including new materials and innovative production processes, for example, polymeric matrix, orodispersible, 3D printing, MUPs, etc. The heterogeneity and complexity of these tablets go well beyond a traditional gastroresistant coating tablet, making orientations on the practice of tablet subdivision difficult. This editorial aims to provide a critical and up-to-date evaluation of this scenario based on the most recent studies involving the subdivision of modified-release tablets.

In vitro release and in vivo pharmacokinetics in Beagle dogs of pregabalin sustained-release tablets / 国际药学研究杂志

Objective: To evaluate the in vitro release degree, release mechanism and dose dumping of test tablet and reference tablet Lyrica® CR. The in vivo pharmacokinetics of the test tablet and the reference tablet were further investigated using the Beagle dog as a model. Methods: With Pfizer's pregabalin sustained-release tablets(Lyrica® CR)as the reference listed drug, the in vitro release behavior was evaluated using an automatic dissolution apparatus, and similarity factor(f2)method was used to analyze the in vitro release similarity between the reference tablet and the test tablet. The in vitro release equation was fitted to evaluate the drug release mechanism. Study was conducted on dose dumping of preparations based on the relevant guiding principles of the United States, Europe and China. Finally, the pharmacokinetic parameters of the test tablet and the reference tablet in Beagle dogs were compared. Results: The f2 of the test tablet and the reference tablet were more than 80 in all five release media, and there was no sudden release in the release medium containing ethanol. The pharmacokinetic parameters of the reference tablet and the test tablet were as follows: The Tmax was(6.00±2.19)and(4.00±2.19)h, the Cmax was(19.35±11.43)and(17.25±7.77)μg/ml, and the AUC0-t was(340.37± 220.66)and(281.65 ± 196.25)h•μg/ml for the reference tablet and the test tablet, respectively. Conclusion: In this study, the release curve of the test tablet was similar to that of the reference tablet in the five media. The drug was released slowly without sudden release, and the release mechanism in vitro was similar. There was no significant difference in pharmacokinetic parameters between the test tablet and the reference tablet in beagle dogs, and the relative bioavailability was more than 80%.

Pharmacokinetic study on six active ingredients of Qikui Sustained-release Tablets in rabbit plasma / 中草药

Objective: To compare the differences in pharmacokinetic behavior of six ingredients in Qikui Sustained-release Tablets in rabbit plasma. Qikui Granules was taken as reference. Methods: Diazepam was used as internal standard. LC-MS/MS detection methods of astragaloside, hyperin, isoquercitrin, rutin, morroniside, and loganin in rabbit plasma were established, and pharmacokinetic parameters of six components were calculated. Results: Six active ingredients’ equation of linear regressions were: astragaloside Y = 1.0 × 10-4 X - 0.009 9 (r = 0.999 7), morroniside Y = 1.0 × 10-4 X + 0.038 7 (r = 0.999 4), loganin Y = 3.0 × 10-5 X + 0.008 7 (r = 0.999 3), hyperin Y = 1.0 × 10-3 X - 0.016 1 (r = 0.999 0), rutin Y = 5.0 × 10-4 X - 0.011 5 (r = 0.999 4), isoquercitrin Y = 1.7 × 10-3X - 0.307 5(r = 0.999 2). Intra-day and inter-day precision and accuracy and recovery rate were up to the mustard. After Qikui Sustained-release Tablets and Qikui Granules being given by gavege, the maximal concentration (Cmax) of morroniside, loganin, astragaloside, rutin, hyperin, and isoquerctirin in Qikui Granules were (1.333 ± 0.051), (1.238 ± 0.164), (0.83 ± 0.079), (0.127 ± 0.017),(0.444 ± 0.048), and (0.223 ± 0.048) mg/L, t1/2 were (3.848 ± 0.311), (3.822 ± 0.757), (4.982 ± 1.14), (3.73 ± 0.298), (4.732 ± 0.642), and (5.132 ± 0.901) h, respectively, AUC(0-t) were (3.069 ± 0.307), (2.891 ± 0.943), (2.079 ± 0.306), (0.313 ± 0.068), (1.087 ± 0.177), (0.496 ± 0.129) mg∙h/L, respectively, Cmax of morroniside, loganin, astragaloside, rutin, hyperin, and isoquerctirin in Qikui Sustained-release Tablets were (0.985 ± 0.13), (0.961 ± 0.175), (0.693 ± 0.101), (0.094 ± 0.012), (0.354 ± 0.045), (0.201 ± 0.037) mg/L, t1/2 were (4.691 ± 0.337), (5.62 ± 1.64), (6.408 ± 0.707), (4.103 ± 0.341), (6.048 ± 0.882), (5.803 ± 0.59) h, AUC(0-t) were (5.191 ± 1.046), (6.168 ± 1.25), (4.293 ± 0.823), (0.485 ± 0.103), (1.84 ± 0.432), (0.924 ± 0.19) mg∙h/L. Contrast with Qikui Granules, relative bioavailability of morroniside, loganin, astragaloside, rutin, hyperin, and isoquerctirin in Qikui Sustained-release Tablets were 169.1%, 213.3%, 206.5%, 156.0%, 169.3%, and 186.3%, respectively. Conclusion: Qikui Sustained-release Tablets can significantly improve the bioavailability of each active ingredient in rabbit.