Early application of tacrolimus extended-release capsule after kidney transplantation / 器官移植

Objective To evaluate the efficacy and safety of tacrolimus extended-release (Tac-ER) in the early stage after kidney transplantation. Methods Clinical data of 68 recipients undergoing kidney transplantation from 34 pairs of renal allografts were retrospectively analyzed. Two recipients who received bilateral kidneys from the same donor were treated with Tac-ER (Tac-ER group) and tacrolimus immediate-release (Tac-IR) (Tac-IR group) as one of the basic immunosuppressant. The changes of tacrolimus dosage and blood concentration, intra-patient variability (IPV), renal function, incidence of acute rejection, recipient and allograft survival rates and adverse events were statistically compared between two groups. Results The average daily dose of tacrolimus in the Tac-ER group was significantly higher than that in the Tac-IR group (F=8.386, P=0.005). In the Tac-ER group, the mean trough concentration at postoperative 4 d was (6.14±4.04) ng/mL, did not reach the target concentration, significantly lower than (9.41±5.47) ng/mL in the Tac-IR group (F=7.854, P=0.007). In the Tac-ER group, the IPV of trough concentration of tacrolimus within postoperative 1 month was significantly higher than that in the Tac-IR group (0.44±0.15 vs. 0.36±0.12, P=0.032). At postoperative 6 months, there was no significant difference in the renal function between two groups [serum creatinine level was (126±26) μmol/L vs. (120±28) μmol/L, and the estimated glomerular filtration rate was (56±13) mL/(min·1.73 m2) vs. (60±15) mL/(min·1.73 m2), both P > 0.05]. The allograft and recipient survival rates were 100% in both groups. The incidence of acute rejection within postoperative 1 month was 18% in the Tac-ER group and 3% in the Tac-IR group, with no significant difference (P > 0.05). The overall incidence of adverse events was 94% in the Tac-ER group and 97% in the Tac-IR group, with no significant difference (P > 0.05). Conclusions The efficacy and safety of Tac-ER are equivalent to those of Tac-IR, whereas a higher dose of Tac-ER should be orally given to reach the blood concentration similar to that of Tac-IR. During early-stage drug treatment, Tac-ER should be orally given before kidney transplantation or inittally with loading dose, aiming to increase the systemic exposure to tacrolimus early after kidney transplantation and prevent acute rejection caused by insufficient exposure.

Portable and automated analyzer for rapid and high precision in vitro dissolution of drugs / 药物分析学报

We developed a novel portable and automated dissolution test analyzer for rapid and high precision in vitro dissolution testing of drugs.The analyzer consists of a flow-through-cell drug dissolution system,an automated sequential sampling system,a high-speed capillary electrophoresis (HSCE) system,and a data acquisition system.Combining the high-temporal resolution flow-gating sampling approach with HSCE,which has outstanding advantages of efficient separation and resolution,the analyzer can achieve rapid analysis and exhibits the ability in miniaturization for on-site assessment of different active pharmaceutical ingredients.To integrate the flow-through-cell dissolution system with HSCE,a specially designed flow-gating-injection (FGI) interface was employed.The performance of the analyzer was investigated by analyzing the dissolution of immediate-release drugs including single dose (amoxicillin dispersible tablets) and fixed dose combination (amoxicillin and clavulanate potassium) drug tablets with the high-temporal resolutions of 12 s and 20 s,respectively.The dissolution profiles of different active pharmaceutical ingredients could be simultaneously and automatically monitored with high repeatability and accuracy.The analyzer was successfully utilized for the pharmaceutical quality control and bio-relevant dissolution testing,as well as in vivo-in vitro correlation analysis.Our portable analyzer is miniaturized,convenient and of low-cost,and will provide a valuable tool for dissolution testing in pharmaceutical research and development.

Optimization Of Roll Compactor Variables And Formulation Of Anti-Retroviral Tablet By Roll Compaction Method

Objective: This study emphasis on roll compaction variable and how the processing parameters influence the formation of granules in process of formulations of antiretroviral IR Tablet with help of optimization technique. Methods: In this present work we aimed to develop a stable pharmaceutical dosage form with anti-retroviral drug tenofovir disoproxil fumarate. % retention of granules over # 60 mesh in roll compaction method by sizing with 50G co-mill screen was assessed by optimization and results were evaluated by Design expert 12.0 software. Various parameters and optimization of the parameter for formulation for better product was done by using 23 factorial design and dry granulation technique for manufacturing tablets. Three operating parameters the roller speed, the hydraulic pressure and the gap width on the Chamunda CPMRC-200/150 Roll Compactor were varied. The planned response variable for study was % retention over #60 ASTM mesh. % retention of granules was calculated by weighing granules on digital electronic balance with respect to how much premix material was taken for compaction. Results: Excipients compatibility study gave positive way showing no change in physical appearance of drug-excipients mix. It reviled that drug was compatible with excipients used. By formation of granules with required ratio, the value of Compressibility index changed from 29 to 21.89, showed that flow properties were improved i.e. from poor to passable. Design expert 12.0 gave optimized solution for formation of required quantity of granules. Pareto chart showed envaulted positive and negative impact of factors on response as explained in results. The results clearly indicate that how granules manufacturing in roll compaction process are influenced by roller pressure, roller gap and speed. 70 % flakes formation and granules retention were observed with 4000 kg/cm2 pressure, 1 mm roller gap width and 6 rpm speed of roller. Pareto chart clearly indicate major impact is of roller pressure. Comparative dissolution profile graph showed that drug release pattern is similar with the innovator tablet. A stable, robust tablets were formed at the end of process. Conclusion: In this study, by optimizing processing variables stable antiretroviral immediate release oral solid dosage form was formed.

Efficacy of Fentanyl Buccal Tablets for Patients Who Cannot Retain at the Above a Rear Molar between the Upper Cheek and Gum

Fentanyl buccal tablets place the tablet at the buccal site (above a rear molar, between the upper cheek and gum) and wait until it dissolves, but some patients may not be able to retain it due to defects of the maxillary molars. The aim of this study was to evaluate the effectiveness and safety of fentanyl buccal tablets when they were used outside the buccal site. Seven patients were treated with fentanyl buccal tablets outside the buccal site. For each of 5 episodes in which effective dose was identified, were investigated to average pain intensity assessed on a 0 to 10 numerical rating scale at 30 min postadministration and reduction in pain intensity of more than 33%. Pain intensity significantly decreased at 30 min postadministration in 5 patients with effective doses identified (p<0.001). In 92.0% of episodes treated, there was a reduction in pain intensity of more than 33%. Adverse events were somnolence and nausea with mild. However, these effects did not result in discontinuation of medication. Our findings suggested that fentanyl buccal tablets can be used effectively and safely even when patients used outside the buccal site.

Comparative In Vitro Dissolution Study On Metformin Market Products Using Different Dissolution Apparatuses

Objective: This study was proposed to evaluate and compare the in vitro dissolution profiles of six Metformin Hydrochloride (MH) market products. Methods: Different dissolution apparatuses (USP apparatus II, IV and beaker method) were used to evaluate the dissolution profiles (in phosphate buffer, pH 6.8) of two immediate release (IR) generic products of Metformin Hydrochloride (MH): Cidophage® 1000 mg (G1, Egyptian market) and Metformin arrow® 1000 mg (G2, French market) with respect to the reference products named Glucophage® 850 mg (R1, Egyptian market and R2, French market). In addition to a generic controlled-release (CR) product; Cidophage Retard® 850 mg (G3) versus the reference product; Glucophage XR® 1000 mg (R3) (both from Egyptian market). Dissolution efficiency (D. E.) and the similarity factor (f2) were calculated. Weight uniformity, hardness, tablet dimensions and MH content were measured. Results: Results of the three apparatuses showed that MH IR products studied (reference and generics) did not meet the 75% USP 30 specifications for MH dissolved at 30 min. For MH CR products, Glucophage XR® did not fulfill the USP release criteria, while Cidophage Retard® did. USP apparatus IV revealed the highest sensitivity and discriminative capability. Conclusion: Generally, MH IR generics (G1 and G2) might be interchangeable with the innovator product (Glucophage®). However, Cidophage Retard® might not be interchangeable with Glucophage XR®.

Formulation and pharmacopoeial quality evaluation of ketorolac tromethamine IR tablet and comparison with marketed product

This study describes the formulation of immediate release Ketorolac tromethamine (KT) 10-mg tablet by directcompression method; evaluation of their compliance to various Pharmacopoeial quality parameters, i.e., weightvariation, friability, hardness, thickness, moisture content, disintegration, assay, and dissolution; and their comparisonwith marketed brands for determination of pharmaceutical equivalency. Five formulations of KT were prepared(coded as FKT1, FKT2, FKT3, FKT4, and FKT5) by direct compression method using different superdisintegrants.Micrometric properties of the mixtures of the drug and the excipients prepared for formulation were evaluated. Qualityevaluation of the five different formulations and randomly selected four different brands of KT 10-mg tablets purchasedfrom the local market (coded as LKT1, MKT2, MKT3, and SKT4) were performed according to Pharmacopoeia. Theresults were obtained by UV-Vis spectrophotometer and all the dissolution profiles were characterized by the zeroorder kinetics. All the brands of KT and developed formulations met the official specification except SKT4 whichshowed excessive moisture content of 7.18%. None of the tested brands of KT were found to be pharmaceuticallyequivalent, whereas two developed formulation were pharmaceutically equivalent with the in house benchmark(MKT2) from which their interchangeability can be suggested.

Meta-analysis of Efficacy and Safety of Tapentadol Immediate-release Preparation for Relie ving Moderate and Severe Acute Pain after Brachiocephalic Arteritis / 中国药房

OBJECTIVE： To systematically evaluate the efficacy and safety of Tapentadol immediate-release preparation （Tap IR） for relieving severe acute pain after brachiocephalic arteritis， and to provide evidence-based reference for rational drug use. METHODS： Retrieved from PubMed， Medline， Cochrane library， CNKI， VIP， Wanfang database and American clinical trial database， randomized controlled trials （RCTs） about Tap IR （trial group） versus Oxycodone immediate-release preparation or placebo for relieving severe acute pain after brachiocephalic arteritis were collected. After literature screening， data extraction and literature quality evaluation with modified Jadad scale， Meta-analysis was conducted by using RevMan 5.3 software. RESULTS： A total of 6 RCTs were included， involving 2 378 patients. Results of Meta-analysis showed that 48 h total pain relief value （TOTPAR48） of trial group was significantly higher than control group [MD＝35.60，95％CI（27.31， 43.88）， P＜0.000 01]. Results of sub-group analysis showed that TOTPAR48 of trial group using Tap IR 50 mg [MD＝28.68， 95％CI （18.18， 39.17），P＜0.00 001]， 75 mg [MD＝39.97， 95％CI （34.21， 45.73）， P＜0.000 01] and 100 mg[MD＝38.50， 95％CI（1.46， 75.54），P＝0.04] were significantly higher than control group； TOTPAR48 of patients who received Tap IR 75 mg were significantly higher than patients who received Tap IR 50 mg [MD＝9.04，95％ CI（4.31， 13.77），P＝0.000 2]. There was no statistical significance in the utilization rate of rescue medicine （URM） between 2 groups [RR＝1.23，95％ CI（0.84， 1.80），P＝0.29]. Subgroup analysis showed that URM in patients who received Tap IR 75 mg was significantly lower than those receiving Tap IR 50 mg [RR＝0.62，95％CI（0.41， 0.94），P＝0.02]. The total difference of 48 h pain intensity （SPID48） in trial group was significantly lower than control group [MD＝－18.96，95％CI（－37.28，－0.64），P＝0.04]. Subgroup analysis showed that SPID48 in patients who received Tap IR 75 mg was significantly higher than those receiving Tap IR 50 mg [MD＝21.66，95％CI（8.93， 34.39），P＝0.000 9]. There was no statistical significance in the total change of pain impression （PGIC） between 2 groups [RR＝0.95，95％CI（0.88， 1.03），P＝0.23]. Subgroup analysis showed that PGIC in patients who received Tap IR 75 mg was significantly higher than those receiving Tap IR 50 mg [RR＝1.07，95％CI（1.01， 1.13），P＝0.02] but significantly lower than those receiving Tap IR 100 mg [RR＝0.86，95％CI（0.77， 0.97），P＝0.01]. The incidence of nausea， vomiting， constipation， dizziness and headache in trial group were significantly lower than control group （P＜0.05）. CONCLUSIONS： Tap IR shows good therapeutic efficacy and safety for severe acute pain after brachiocephalic arteritis， and the efficacy of Tap IR might be better when the dose of Tap IR is 75 mg.

Comparison of Efficacy and Tolerability of Immediate Release Glucosamine HCL And Glucosamine HCL Sustained Release Formulation in the Treatment of Knee Osteoarthritis; A Randomised Clinical Trial

Background: Osteoarthritis (OA) is the most common form of and a leading cause of chronic disability between fourth and fifth decade of life, with a prevalence ranging between 17-60.6% in India. Objective: To compare the efficacy and safety profile of glucosamine HCl- sustained release (GLU-SR) with that of Glucosamine HCl- immediate release (GLU-IR) in patients with knee osteoarthritis (OA). Methods: This was an open labelled, randomised, controlled trial conducted in a tertiary care hospital at Kanpur. The study involved 60 patients with knee OA, randomised to receive single oral dose of 1,500 mg GLU-SR and GLU-IR for 60 days with 30 patients in each group. The primary efficacy being reduction in pain and improvement in function was assessed using visual analogue scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. Intention-to-treat principle, repeated measure of ANOVA and mixed model analysis were used for statistical analysis. The history of adverse reactions experienced was collected throughout the study period. Results: There was a significant reduction in algo functional indices as primary outcome measure in both the groups (P < 0.001). A significant difference (P < 0.05) in the number of patients reporting ADR in the GLU-SR arm (38% lesser) was noted as compared to GLU-IR arm, with no difference in the use of rescue medications in both arms. Conclusions: From the observations made in this study it is concluded that GLU-SR is as effective as GLU-IR in the management of knee OA; with an advantage of having a better safety profile.

Influence of genetic polymorphisms in drug metabolism enzymes and transporters on pharmacokinetics of different fluvastatin formulations / 中国药理学与毒理学杂志

OBJECTIVE The purpose of the present study was to investigate the impact of fluvas-tatin formulation on the pharmacokinetics-genetic polymorphis relationship. METHODS We compared the difference between the pharmacokinetics of fluvastatin as an extended-release (ER) 80 mg tablet and an immediate-release(IR)40 mg capsule in terms of drug metabolism enzyme and transporter ge-netic polymorphisms. In this open-label, randomized, two-period, two-treatment, crossover study, ef-fects of BCRP, SLCO1B1, MDR1, CYP2C9, and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed in 24 healthy individuals.Each treatment duration was 7 days with a washout period of 7 days between the crossover.Serum concentration of fluvastatin was evaluated using high-performance liquid chromatography-tandem mass spectrometry. RESULTS The SLCO1B1 T521C genotype had no statistically significant effect on IR 40 mg capsule of fluvastatinafter single or repeated doses.However,for the ER 80 mg tablet,the SLCO1B1 T521C genotype correlated with the AUC0-24of repeat doses (P=0.01). The CYP2C9*3 genotype correlated with the AUC0- 24after the first dose IR 40 mg capsule (P<0.05); however, the difference between CYP2C9*1/*1 and CYP2C9*1/*3 was not statistically significant after repeated doses. CONCLUSION The effect of SLCO1B1 T521C on fluvas-tatin exposure was observed and was more profound in ER and repeated dose administration than in IR and single dose administration.We recommend that formulation should be incorporated into future pharmacogenomics studies and clinical implication guidelines.

Cinitapride Extended-Release Tablets Versus Cinitapride Immediate-Release Tablets in the Treatment of Functional Dyspepsia and Gastroesophageal Reflux Disease : A Randomized Clinical Trial.

Prokinetics are commonly used for Functional Dyspepsia (FD) and GastroEsophageal Reflux Disease (GERD). Aims and Objectives: To evaluate the safety and efficacy of cinitapride Extended-Release (ER) tablets versus conventional cinitapride Immediate-Release (IR) tablets for the treatment of FD and GERD. Materials and Methods: Patients with FD and GERD received either cinitapride ER 3 mg tablets OD or cinitapride IR 1 mg tablets TID for 4 weeks in this randomized, multicentre study. Change in the mean intensity score of gastrointestinal (GI) symptoms (overall and individual) at the end of the study and at each weekly follow up visit as compared to baseline, patients with complete resolution of GI symptoms, patients with > 50% reduction from baseline in overall intensity score, rescue medication use and overall efficacy were recorded. The safety variables were reported adverse events (AEs), laboratory parameters, electrocardiogram, and overall tolerability. Unpaired t test, chi square test or Fisher’s exact test were used for analysis. p < 0.05 was considered significant. Results: Total 218 patients were enrolled Cinitapride ER tablets were non-inferior (non-inferiority margin -2.5) to cinitapride IR tablets for the change in the mean overall GI symptom intensity score at the end of the study as compared to the baseline (treatment difference - 0.2 (95% CI: -2.2, 1.7)); also, no significant difference was found for other efficacy variables (p > 0.05). Eight AEs of mild-to-moderate intensity were reported. There was also no difference in the overall tolerability between the study groups (p = 0.875). Conclusions : Both the study treatments were comparable in terms of safety and efficacy for the treatment of FD and GERD.

Application of k-carrageenan in valsartan immediate-release pellets by extrusion-spheronization / 中国药科大学学报

@#The aim of the study was to select a suitable pelletisation aid of valsartan immediate-release pellets in the extrusion process and optimized the formulation. The properties of the pellets with five excipients which were microcrystalline cellulose(MCC), low-substituted hydroxypropyl cellulose(L-HPC), crospovidone(PVPP), pregelatinized starch(PCS)and k-carrageenan were evaluated and compared by the single factor test. And the pelletisation aids were chosen preliminary. The properties of the pellets with MCC, L-HPC, k-carrageenan respectively were evaluated and compared and k-carrageenan was determined as the most appropriate pelletisation aid. The Box-Behnken design was employed to optimize the formulation. The optimised formulation was k-carrageenan 16. 98 g, HPMC-E5 2. 03 g, SLS 0. 26 g. The yield and aspect ratio of pellets was 91. 23% and 1. 14, respectively. And there was no significant difference between observed and predictive responses. The results showed k-carrageenan pellets owned properties of a high yield, acceptable sphericity and fast drug release.

Comparative Evaluation of the Disintegrant Properties of Rice Husk Cellulose, Corn Starch and Avicel in Metronidazole Tablet Formulation.

Cellulose is a polysaccharide that has been employed in pharmaceutical applications over the years. However, the quest for waste management and an alternative to imported raw materials for locally manufactured drug products necessitated this study. This study was undertaken to explore the application of cellulose extracted from waste, rice husk as a disintegrant in the formulation of metronidazole tablets for immediate release. Cellulose was extracted from rice husk and characterized. Thereafter, a comparative characterization of the attributes of the tablets formulated was undertaken using Corn Starch, microcrystalline cellulose and rice husk as disintegrants. The granules were characterized for flow properties and tablets were evaluated for crushing strength, friability, disintegration and in vitro drug release. The tablets formulated with rice husk cellulose were found to be bioequivalent to those of corn starch which is a standard in comparative studies of disintegrants. Hence, rice husk cellulose is an alternative excipient to explore as a pharmaceutical excipient for limited resource economies.

Fed Bioequivalence Studies for Immediate Release Drug Products: Beneficial or Wastage.

Aims: The present study was undertaken to understand the need of fed bioequivalence studies for immediate release pharmaceutical products and thereby evaluating the relative appropriateness of guidelines given by the European Medicines Agency (EMA) and the United States Food and Drug Administration (USFDA). Vulnerability to show bioequivalent or non-bioequivalent results on the basis of type of drugs was also assessed. Study Design: The present work is a meta-analysis involving 162 bioequivalence studies conducted on healthy human subjects. Place and Duration of Study: Accutest Research Laboratories (I) Pvt Ltd, A-31, Khairne MIDC, TTC Industrial Area, Khairne, Navi Mumbai, 400 709, India, between June 2013 and February 2014. Methodology: The present meta-analysis included a total of 162 bioequivalence studies of which 81 were conducted under fasted condition and the other 81 studies were conducted under fed condition. The drug products were fixed dose combinations and mono drug products for 22 and 140 studies respectively representing all the classes of Biopharmaceutics Classification System (BCS). The bioequivalence was assessed by standard criteria laid down by regulatory authorities. The results were correlated with the respective condition of study (fasted or fed) and the corresponding BCS class of the drug product. The observations were discussed in the light of available literature. Results: A total of 78 and 74 studies conducted under fasting and fed conditions respectively had bioequivalent results. All studies conducted on fixed dose combination products had bioequivalent results. Five drug products had bioequivalent results only under fasting condition which proportionately contributed to 6.17% (5/81 fasting studies). These drug products complied only with the EMA guidelines and not USFDA defined passing criteria. All drug products belonging to BCS classes I and III showed bioequivalent results whereas drug products belonging to BCS class IV contributed to 80% of the total non-bioequivalent studies. Conclusion: The EMA approach can be followed for BCS class I drugs while USFDA approach looks better for remaining drug products. Further research work is required to confirm the trend observed in our meta-analysis.

Formulation design and evaluation of Cefuroxime axetil 125 mg immediate release tablets using different concentration of sodium lauryl sulphate as solubility enhancer

Cefuroxime axetil immediate release tablets were formulated by direct compression method with different percentages of sodium lauryl sulphate (SLS) such as 0.5, 1.0, 1.5 and also without SLS. Resulting batches of tablets were evaluated by both pharmacopeial and non-pharmacopeial methods to ascertain the physico-mechanical properties. Dissolution test were carried out in different medium like 0.07 M HCl, distilled water, 0.1M HCl of pH 1.2 and phosphate buffers at pH 4.5 and 6.8 to observe the drug release against the respective concentration of SLS used. Later, test formulations were compared by f1 (dissimilarity) and f2 (similarity) factors using a reference brand of cefuroxime axetil. Significant differences (p<0.05) in dissolution rate were recorded with the change in concentration of SLS in different media. Test formulation T3 containing 1% SLS was found to be best optimized formulation based on assay, disintegration, dissolution and similarity and dissimilarity factors.

Formularam-se comprimidos de liberação imediata à base de cefuroxima axetil, pelo método de compressão direta, com diferentes percentagens de lauril sulfato de sódio (LSS), tais como 0,5, 1,0, 1,5, e também sem SLS. Os lotes resultantes dos comprimidos foram avaliados por ambos os métodos da farmacopeia e não farmacopeicos para determinar as propriedades físico-mecânicas. O teste de dissolução foi realizado em meios diferentes, como HCl 0,07 M, água destilada, HCl 0,1 M com pH 1,2 e os tampões fosfato (pH 4,5 e 6,8) para observar a liberação do fármaco contra a correspondente concentração de LSS utilizado. Em seguida, as formulações de teste foram comparadas por fatores f1 (dissimilaridade) e f2 (similaridade), utilizando uma marca de referência de cefuroxima axetil. Diferenças significativas (p<0,05) na taxa de dissolução foram registradas com a mudança na concentração de LSS em diferentes meios de dissolução. A formulação T3 contendo LSS a 1% foi considerada a melhor formulação otimizada com base nos ensaios de desintegração, dissolução e fatores de semelhança e dissimilaridade.

Formulation and Evaluation of Bi-layered Sustained Release Matrix Tablets of Tramadol Hydrochloride.

Bi-layer tablets of tramadol hydrochloride were prepared by direct compression technique incorporating an immediate release layer and a sustained release layer. An immediate release layer was successfully designed to release the bolus dose instantaneously. Water soluble Xanthan gum, water insoluble Kollidon SR and Eudragit L 100 were used as carriers in the sustained release layer of the matrix tablet. All the tablets were evaluated for thickness, diameter, weight variation, hardness and friability. The in vitro drug release was studied for eight hour, first two hours dissolution in acidic medium followed by six hour dissolution in buffer medium. Matrix tablet showed a sustained release rate with a controlled fashion as a function of the quantity of polymer used. The in vitro drug release data were fitted with several mathematical models and mean dissolution time along with fractional dissolution time values (T25%, T50% and T80%) were calculated. Xanthan gum was found to be the most effective rate retarding agent compared to Kollidon SR and Eudragit L 100, when used at same ratio in the formulations.

Combined system of sinomenine hydrochloride sustained-release pellets / 中国药科大学学报

Aim: To establish a linear additive model for the predication of in vitro sinomenine hydrochloride release from the combination of immediate release, enteric-coated and sustained-release pellets based on the release profiles of each pellet type. Methods: Immediate release pellets were manufactured by extrusion/spher-onization technology. The operation of bottom-spraying in the fluid-bed equipment was conducted to enteric-coating using Eudragit~(R) L-30D-55 and sustained-release coating using Surelease~(R) . In vitro sinomenine hydrochloride release profiles of both uncoated and coated pellets were fitted to the chosen mathematical equations offered by the curve fitting toolbox of Matlab~(R) before a linear additive model was created based upon the best-to-fitting equations. The proportion of each pellet type in the combined format to generate the desired 24 h sinomenine hydrochloride release profile was solved by Matlab~(R). The predicted and assayed sinomenine hydrochloride release from the polled pellets was compared. Results: It was shown that the actual sinomenine hydrochloride release profiles of each pellet type were approximate to those of predicted ones. A linear additive model of the appropriate mathematical equations of each pellet was proven to be capable of controlling in vitro release of sinomenine hydrochloride multiple-unit pellets. Conclusion: A multiple-unit combined system of the selected pellets, as a novel sustained-release system, was successfully prepared. In vitro release performance of the calculated combination of each pellet type could be guaranteed by this approach in designing sustained-release drug delivery system.