Influence of Xiaoshuan enteric-coated capsules + aniracetam therapy on cerebral blood perfusion and nerve function in patients with convalescent cerebral infarction

Objective: To investigate the influence of Xiaoshuan enteric-coated capsules + aniracetam therapy on cerebral blood perfusion and nerve function in patients with convalescent cerebral infarction. Methods: A total of 177 cases of patients with convalescent cerebral infarction were retrospectively reviewed and then divided into the control group (n=109) and the Xiaoshuan enteric-coated capsules group (n=68). Control group received aniracetam therapy on the basis of routine treatment, and Xiaoshuan enteric-coated capsules group received Xiaoshuan enteric-coated capsules + aniracetam therapy on the basis of routine treatment. The differences in ultrasound cerebral blood perfusion parameter levels as well as serum neurotrophy index and nerve injury index contents were compared between the two groups. Results: Before treatment, there was no statistically significant difference in ultrasound cerebral blood perfusion parameter levels as well as serum neurotrophy index and nerve injury index contents between the two groups. After treatment, ultrasound cerebral blood perfusion parameters PSV and TMV levels in Xiaoshuan enteric-coated capsules group were higher than those in control group whereas RI level was lower than that in control group;serum neurotrophy indexes bFGF, BDNF and VEGF contents were higher than those of control group;serum nerve injury indexes GFAP, NSE, UCH-L1 and S100B contents were lower than those of control group. Conclusion: Xiaoshuan enteric-coated capsules + aniracetam therapy can significantly increase cerebral blood perfusion and optimize nerve function in patients with convalescent cerebral infarction.

Pharmacokinetic Evaluation of Chitosan-Succinyl-Prednisolone Conjugate Microparticles as a Colonic Delivery System: Comparison with Enteric-Coated Conjugate Microparticles

In the previous study, chitosan-succinyl-prednisolone conjugate microparticles (MP) were found to exhibit good efficacy and reduced toxicity nearly as well as their Eudragit L-coated microparticles (MP/EuL). This proposes a question whether enteric-coating of MP is necessary or not. Although MP/EuL were already examined for their pharmacokinetic and gastrointestinal behaviors, MP have not been done yet. Therefore, in this study, MP were evaluated by investigating pharmacokinetic features in detail. MP with the in vitro features equivalent to those of the previous conjugate microparticles could be produced more readily in the modified preparative method. Pharmacokinetic and gastrointestinal behaviors of MP were investigated by intragastric dosing (5 mg PD eq./kg) to rats with 2,4,6-trinitrobenzenesulfonic acid-induced ulcerative colitis. The plasma concentration was suppressed extensively in MP as well as MP/EuL, supporting the reduction of PD systemic toxic side effects. However, the plasma level increased gradually up to 7 h in MP, but not in MP/EuL. At 8 h after dosing, MP were detected in the stomach to a fair extent, and free PD was found there, indicating that MP were subjected to trapping in the stomach probably due to positive charge of chitosan molecules. For MP, such prolonged localization and slow release of PD in the stomach were probably associated with the gradual increase in plasma concentration. Therefore, MP/EuL were evaluated to be superior to MP for effective targeting to ulcerative colitis. It is concluded that enteric-coating is very important for the targeting system using MP.

Formulation Optimization Utilizing D-Optimal Experimental Design of Oral Capsules Containing Enteric-Coated Pellets of Lansoprazole and<i>in vivo </i>Bioequivalence

An optimized formulation of capsules containing Lansoprazole enteric-coated pellets using D-Optimal design with a polynomial statistical model were prepared by using Eudragit?L100 as an enteric coated polymer to provide resistance to simulated gastric acid dissolution in buffer media. D-Optimal experimental design was used to determine the optimal level for three coating layers that were applied to formulate the enteric-coated pellets including a drug loading layer, a sub-coating, and an outer enteric coating. Dissolution studies were performed on the prepared Lansoprazole capsules. Less than 5 percent of Lansoprazole was released in 60 minutes in an acidic dissolution medium (pH 1.2) and greater than 90 percent of active ingredient was released in the next 60 minutes in a buffer dissolution medium (pH 6.8). The Lansoprazole capsules were stable with no observable change in physico-chemical properties in accelerated and normal storage conditions for 6 and 18 months, respectively. The pharmacokinetic parameters Cmax, Tmax, AUC0-t, and AUC0-∞ were determined after administration of the D-Optimal design optimized capsules of LPZ to healthy beagle dogs and were statistically compared to Gastevin? capsules as a reference (KRKA, Slovenia) using the non-compartmental method with the aid of WinNonlin 5.2 software. The analysis of variance showed that the two formulations did not demonstrate bioequivalence using a 90% confidence interval range (80% - 120%) of Cmax, AUC0-t, and AUC0-∞. No significant difference in Tmax was found at the 0.95 significance level using the Wilcoxon signed-rank test. D-Optimal Experimental Design provided definitive direction for an optimal formulation of capsules containing enteric-coated pellets of lansoprazole loaded within the coating of pellets that provided similar bioequivalence to Gastevin.

Nonlinear relationship between enteric-coated mycophenolate sodium dose and mycophenolic acid exposure in Han kidney transplantation recipients

The aim of the research was to investigate the pharmacokinetics(PK) of enteric-coated mycophenolate sodium(EC-MPS) by quantification of the active metabolite of mycophenolic acid(MPA)after multiple escalating oral doses in Han kidney transplant recipients. A total of 28 Han postoperative kidney transplant recipients were given a multiple-dose of 540, 720 or 900 mg of EC-MPS two times a day in combination with tacrolimus for 6 days. Blood specimens were collected at each time point from0 to 12 h after EC-MPS administration. MPA plasma concentrations were measured by UPLC–UV. The relationship between the EC-MPS dose and its PK parameters was assessed. In the range from 540 to900 mg, C_(max) and AUC_(0–12h) did not increase with dose escalation. The AUC_(0–12h), C_(max), C_0 and T_(max) for the 540 720 and 900 mg doses were not significantly different, respectively(P 40.05). AUC_0–12 h and C_(max) were increased less than proportionally with increasing EC-MPS dose levels. Inter-individual variability in AUC_(0–12h), C_(max) and C_0 were considerable. Nonlinear PK relationships were found from the doses of 540–900 mg of EC-MPS.

Gradient high performance liquid chromatography method for simultaneous determination of ilaprazole and its related impurities in commercial tablets

A methodology(HPLC)proposed in this paper for simultaneously quantitative determination of ilaprazole and its related impurities in commercial tablets was developed and validated.The chromatographic separation was carried out by gradient elution using an Agilent C8 column(4.6 mm×250 mm,5 mm)which was maintained at 25℃.The mobile phase composed of solvent A(methanol)and solvent B(solution consisting 0.02 mmol/l monopotassium phosphate and 0.025 mmol/l sodium hydroxide)was at a flow rate of 1.0 ml/min.The samples were detected and quantified at 237 nm using an ultraviolet absorbance detector.Calibration curves of all analytes from 0.5 to 3.5 mg/ml were good linearity(r≥0.9990)and recovery was greater than 99.5% for each analyte.The lower limit of detection(LLOD)and quantification(LOQ)of this analytical method were 10 ng/ml and 25 ng/ml for all impurities,respectively.The stress studies indicated that the degradation products could not interfere with the detection of ilaprazole and its related impurities and the assay can thus be considered stability-indicating.The method precisions were in the range of 0.41-1.21 while the instrument precisions were in the range of 0.38-0.95 in terms of peak area RSD% for all impurities,respectively.This method is considered stabilityindicating and is applicable for accurate and simultaneous measuring of the ilaprazole and its related impurities in commercial enteric-coated tablets.

Delayed-release oral mesalamine tablet mimicking a small jejunal gastrointestinal stromal tumor:A case report

BACKGROUND Enteric-coated medications are supposed to pass intact through the gastric environment and to release the drug content into the small intestine or the colon.Before dissolution of the enteric coating,they may appear hyperdense on computed tomography(CT).Unfortunately,few reports have been published on this topic so far.In this case report,the hyperdense appearance on contrastenhanced CT of an enteric-coated mesalamine tablet was initially misinterpreted as a jejunal gastrointestinal stromal tumor(GIST).CASE SUMMARY An asymptomatic 81-year-old male patient,who had undergone laparoscopic right nephrectomy four years earlier for stage 1 renal carcinoma,was diagnosed with a jejunal GIST at the 4-year follow-up thoraco-abdominal CT scan.He was referred to our hub hospital for gastroenterological evaluation,and subsequently underwent 18-fluorodeoxyglucose positron emission tomography,abdominal magnetic resonance imaging,and video capsule endoscopy.None of these examinations detected any lesion of the small intestine.After reviewing all the CT images in a multidisciplinary setting,the panel estimated that the hyperdense jejunal image was consistent with a tablet rather than a GIST.The tablet was an 800 mg delayed-release enteric-coated oral mesalamine tablet(Asacol®),which had been prescribed for non-specific colitis,while not informing the hospital physicians.CONCLUSION Delayed-release oral mesalamine(Asacol®),like other enteric-coated medications,can appear as a hyperdense image on a CT scan,mimicking a small intestinal GIST.Therefore,adetailed knowledge of the patients’medications and a multidisciplinary review of the images areessential.

Effect of Weikang Capsule(胃康胶囊)on Aspirin-Related Gastric and Small Intestinal Mucosal Injury

Objective To investigate the effects of Weikang Capsule(胃康胶囊,WKC)on aspirin-related gastric and small intestinal mucosal injury by magnetically controlled capsule endoscopy(MCCE).Methods Patients taking enteric-coated aspirin aged 40-75 years were enrolled in Beijing Anzhen Hospital,Capital Medical University from January 2019 to December 2019.The patients continued taking aspirin Tablet(100 mg per day)and underwent MCCE before and after 1-month combined treatment with WKC(0.9 g per time orally,3 times per day).The gastrointestinal symptom score,gastric Lanza score,the duodenal,jejunal and ileal mucosal injury scores were used to evaluate the gastrointestinal injury before and after treatment.Adverse events including nausea,vomiting,abdominal pain,abdominal distension,abdominal discomfort,dizziness,or headache during MCCE and combined treatment were observed and recorded.Results Twenty-two patients(male/female,13/9)taking enteric-coated aspirin aged 59.5±11.3 years with a duration of aspirin use of 28.0(1.0,48.0)months were recruited.Compared with pre-treatment,the gastrointestinal symptom rating scale scores,gastric Lanza scores,and duodenal mucosal injury scores were significantly reduced after 1-month WKC treatment(P<0.05),and jejunal and ileal mucosal injury scores showed no obvious change.No adverse events occurred during the trial.Conclusions WKC can alleviate gastrointestinal symptoms,as well as gastric and duodenal mucosal injuries,in patients taking enteric-coated aspirin;it does not aggravate jejunal or ileal mucosal injury,which may be an effective alternative for these patients(Clinical trial registry No.ChiCTR1900025451).