In vivo pharmacokinetics and in vitro-in vivo correlation of silymarin phospholipid complex microporous osmotic pump controlled-release tablets in beagle dogs / 药学实践杂志

Objective To evaluate the release characteristics in vitro, pharmacokinetics in rabbits and in vivo-in vitro correlation of silymarin phospholipid complex microporous osmotic pump controlled release tablets（SM-PC MPOP）. Methods The release characteristics of SM-PC MPOP in vitro were detected by HPLC in the artificial gastric fluid. Six beagle dogs were subjected to double cycle cross control, which were given SM-PC MPOP and Legalon（30 mg/kg）. The concentration of silybin in plasma was determined by HPLC and the data were processed by software. Results The cumulative release rate of SM-PC MPOP in vitro was over 85% in 12 h. The pharmacokinetics in beagle dogs showed that SM-PC MPOP and legalon conformed to double compartment first-order absorption model and the pharmacokinetic parameters were obtained: tmax:（3.2±0.4）and（0.9±0.1）h, Cmax:（0.298 6±0.068 9）and（0.629 9±0.076 5）μg/ml, AUC0→24:（2.996 8±0.583 3）and（2.268 9±0.432 8）h·μg /ml. The relative bioavailability of SM-PC MPOP was（162.21 ± 30.82）%. Conclusion SM-PC MPOP could release slowly, which could increase the relative bioavailability significantly. The correlation between the absorption in vivo and release in vitro was fine（r = 0.839 0）.

Optimization of Diltiazem hydrochloride osmotic formulation using QBD approach

Abstract Diltiazem hydrochloride (DLH) is a calcium channel blocker useful for the treatment of angina pectoris, arrhythmia, and hypertension. DLH having a short half-life needs frequent administration for successful treatment but this poses a problem of poor patient compliance. These requirements are served by elementary osmotic pump tablets (EOP) based controlled-release (CR) systems. Quality by design (QbD) approach assists in screening various factors with subsequent assessment of critical parameters that can have a major impact on the scalability of EOP. Tablets were formulated using wet granulation method followed by osmotic coating. Factorial design based QbD strategy aided in defining the risk assessment of influential variables such as hydrophilic polymers and osmotic coat component on the in-vitro release kinetics of the designed EOP tablets. These formulated EOP systems followed zero-order kinetics, a characteristic feature of EOPs. EOP tablets were formulated applying a systematic QbD statistical approach. The formulated DLH EOP systems with improved concentration-independent behavior helped to address the challenges of IR formulation. Application of QbD strategy in ascertaining the scalability of DLH EOP formulation would help pharmaceutical industries in the translation of EOP based drug delivery systems from R&D to market.

Redefinition to bilayer osmotic pump tablets as subterranean river system within mini-earth via three-dimensional structure mechanism

Defining and visualizing the three-dimensional (3D) structures of pharmaceuticals provides a new and important tool to elucidate the phenomenal behavior and underlying mechanisms of drug delivery systems. The mechanism of drug release from complex structured dosage forms, such as bilayer osmotic pump tablets, has not been investigated widely for most solid 3D structures. In this study, bilayer osmotic pump tablets undergoing dissolution, as well as after dissolution in a desiccated solid state were examined, and visualized by synchrotron radiation micro-computed tomography (SR-μCT). In situ formed 3D structures at different in vitro drug release states were characterized comprehensively. A distinct movement pattern of NaCl crystals from the push layer to the drug layer was observed, beneath the semi-permeable coating in the desiccated tablet samples. The 3D structures at different dissolution time revealed that the pushing upsurge in the bilayer osmotic pump tablet was directed via peripheral "roadways". Typically, different regions of the osmotic front, infiltration region, and dormant region were classified in the push layer during the dissolution of drug from tablet samples. According to the observed 3D microstructures, a "subterranean river model" for the drug release mechanism has been defined to explain the drug release mechanism.

Preparation and in vitro release of ivabradine hydrochloride elementary osmotic pump tablets / 中国药科大学学报

@#In this study, ivabradine hydrochloride (IVB) was prepared as elementary osmotic pump tablets whose administration frequency was reduced to once daily. The dissolution method was developed, and effects on drug release profiles were evaluated by single factor analysis involving suspending agents, osmotic active agents and aging process. Orthogonal test was carried out at 3 levels on 3 factors including the amount of polyoxyethylene (PEO) in the core, polyethylene glycol (PEG) percentage and weight increase of controlled-release film coatings. The final formulation consisted of IVB (16.25 mg), PEO N80 (60 mg), hypromellose E5 (10 mg), lactose (111.75 mg), magnesium stearate (2 mg); and the film coatings consisted of PEG (15%), cellulose acetate (85%), with a weight increase of 7.5%. In vitro drug release behaviors were investigated. Prepared tablets exhibited similar release profiles in different pH dissolution media, with no risk of dose dumping in 40% ethanol solutions. The osmotic pressure differences inside and outside the membrane drove drug release. IVB osmotic pump tablets could reduce the frequency of administration and improve patients'' compliance, thus with better application values.

Formulation and stability studies of metformin hydrochloride in a controlled porosity osmotic pump system

This study was designed to formulate, for the first time, metformin hydrochloride (MH, 850 mg/tablet) as a controlledporosity osmotic pump (CPOP) system to achieve zero-order release pattern. MH core tablet was coated with celluloseacetate membrane containing PEG 400. The effect of different percentages and molecular weights of polyethyleneoxide (PEO, 900K and 4M) in tablet core was studied. The United States Pharmacopeia (USP) apparatus II andphosphate buffer pH 6.8 were used for the release studies; meanwhile, a promising formula was tested in biorelevantmedia. The stability of some selected formulations was carried out for 6 months, at bench and accelerated conditions.Evaluation included: MH content, Differential scanning calorimetry (DSC), Scanning electron microscopy (SEM),drug release, and kinetics. Results revealed that increasing PEO percentage within the core decreased MH release.SEM verified formation of pores in the membrane that accounts for MH release. Almost all stored tablets werestable for all studied parameters. MH endothermic peak maintained its position and energy of enthalpy on storageas confirmed by DSC. MH release rate from a promising formula, following zero-order release model, increased by28% in biorelevant media compared to phosphate buffer. Subsequently, in vitro release in biorelevant media could beemployed as a tool to anticipate in vivo tone of CPOP formulations

Development Of Water Transplant Based Single Core Osmotic Pump For Fluvoxamine Maleate Employing Quality By Design Principles

The present study draw a bead on preparing single core osmotic pump with improved water transplant by employing Quality by Design (QbD) principles to achieve zero order drug release for prolonged period of time. QbD principles were employed in preparing single core osmotic pump by deriving quality target product profile (QTPP), critical quality attributes (CQA) followed by risk assessment using ishikawa diagram and risk estimation matrix. Box-Behnken Design was employed to study the effect of various independent parameters like concentration of Natrosol 250 HX (X1) and concentration of Xylitab (X2) no. of orifice (X3), on various dependent parameters like lag time (Y1) and time required for release 25%, 50%, 75% and 100% drug (Y2, Y3, Y4 and Y5). A controlled space was designed where each criteria or CQA was satisfied. Optimized formulation was further characterized for its efficiency. The results of design suggest the suitability of design for optimization of single core osmotic pump. In the initial period, drug release was driven by no. of orifice which on later stage depends on concentration of swellable polymer and concentration of osmogen. Optimized design was validated by preparing check point batch having less than 5% predicted error. Model fitting with drug release kinetics showed that optimized single core osmotic pump released drug in zero order. Stability data suggested that prepared formulation was stable for 3 month period without significant changes in the CQA. Single core osmotic pump using water transplant was successfully developed for a poorly soluble drug using QbD principles.

Preparation and Pharmacokinetics of Huperzine A Micro-porous Osmotic Pump Pellets / 中国药学杂志

OBJECTIVE: To prepare huperzine A micro-porous osmotic pump pellets and to investigate the pharmacokinetic properties in Beagle dogs. METHODS: The extrusion-spheronisation method was used to prepare the core of huperzine A pellets which then coated by fluid-bed coating technology. Central composite design-response surface method was used to optimize the prescription of coating layer.Then Zero-order, First-order and Higuchi equation of cumulative release with time were fitted to study its release characteristics.The commercially available huperzine A tablets were used as reference preparations to investigate the in vivo pharmacokinetics of huperzine A micro-porous osmotic pump pellets, and the bioequivalence of the two preparations were compared. RESULTS: The formula of coating was optimized as followsEC of 61.5%, PEG400 of 10.5%. Zero-order kinetics existed in the release of the pellets in 24 h. Moreover, the osmotic pressure-controlled delivery was greatly responsible for drug release. In vivo study showed that tmax and ρmax of huperzine A micro-porous osmotic pump pellets were significantly lower than that of the reference preparation, and its t1/2 was significantly prolonged compared with the reference preparation, the relative bioavailability was 95.8%. CONCLUSION: Huperzine A micro-porous osmotic pump pellets had a better sustained release effect in the Beagle dog and have a good correlation in vivo.

Key Formulation Considerations of Push-Pull Osmotic Pump (PPOP) Drug Delivery System / 中国药学杂志

OBJECTIVE: Push-pull osmotic pump (PPOP) is one of conventional osmotic pump systems, which has been widely investigated for formulation development of BCS Ⅱ APIs. However, there is still a lack of experimental data based discussions for some key formulation factors of PPOP. Thus, to investigate some key formulation factors by designed experiments and tried to give some recommendations for those considerations in industrial formulation development. METHODS: Nifedipine was selected as the model drug in this study. The hydration & swell rate and strength of three grades of commercialized high molecular weight polyethylene oxide (PEO) were evaluated via swelling volume change using a home-made apparatus and via compression force using texture analyzer, respectively. The effect of different film coating thickness, proportion of osmotic agent in push layer, and ratios of push layer to pull layer were investigated by drug dissolution using USP apparatus Ⅱ as well. RESULTS: The swelling rate and strength of three grades of high molecular weight PEO (POLYOXTM 301, POLYOXTM Coagulant, and POLYOXTM 303) enhanced along with the molecular weight. The difference of swelling rate is not significant (P>0.05), but that of swelling gel strength is significant (P<0.05). Adding osmotic agent, e.g. NaCl, could significantly improve the swelling rate. Thicker coating membrane retarded drug release and as the coating thickness was higher than 180 μm, it caused incomplete drug release (<90%). When the NaCl proportion in push layer was between 10% and 30 %, there was no significant differences among drug dissolution profiles. However, when the percent of NaCl content in push layer was above 50%, the drug release from PPOP became slower and more incomplete (<90%). CONCLUSION: The ratio of DL/PL has significant impact on drug release. The lower the ratio of DL/PL resulted in faster and more complete drug release. For nifedipine case, the ratio of 2 was recommended.

Preparation and in vitro evaluation of pregabalin controlled porosity osmotic pump tablets / 中国药科大学学报

@#In this study, pregabalin controlled porosity osmotic pump tablets which are taken once a day were prepared. Single-factor tests were carried out to investigate the influence of excipients and manufacturing process. The formulation was optimized through orthogonal experiment on three levels of three significant factors including the amount of sodium citrate, and polyethylene glycol 400 and coating weight gain. On the basis of the results of the single-factor tests and the orthogonal experiment, optimal formulation and manufacturing process were obtained. The final tablet formulation contained pregabalin(82. 5 mg), microcrystalline cellulose(40%), sodium citrate(27. 5%), magnesium stearate(0. 5%)and 5% povidone K30 solution as the tablet binder; the coating formulation consisted of cellulose acetrate and 60% of polyethylene glycol 400 as a porogen; the coating weight gain was 3%. In vitro drug release kinetic study suggested that the drug release from controlled porosity osmotic pump tablets was mainly driven by osmotic pressure, which was barely affected by the pH of the release medium. The drug release behavior of the tablets within 12 hours complied with zero-order release rule and the linear correlation coefficient was 0. 991 6. The obtained porosity osmotic pump tablets could effectively slow the drug release rate, reduce concentration fluctuation and improve the safety and convenience for the patients, hence with broad prospects.

Cyclosporin A osmotic pump tablets which can form supersaturated micelles / 药学学报

The poor solubility of cyclosporine A (CsA) in water limits its oral absorption. We prepared CsA/ Soluplus/SDS complex, which can form CsA/Soluplus/SDS supersaturated micelles (CSS-SM) after hydration. Then, We further prepared CSS-SM osmotic pump tablets (CSS-SM-T). CSS-SM had a particle size of 156 nm, where in encapsulation efficiency and drug loading efficiency of CsA were 89.0% and 17.5%, respectively. CSS-SM-T achieved zero-level drug release in vitro. Pharmacokinetic data from Beagle dogs (all animal experiments were conducted under the guidelines approved by the Institutional Animal Care and Use Committee of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences) indicated that CsA in the ordinary osmotic pump tablets was hardly absorbed after orally administered; despite slightly lower bioavailability [relative bioavailability: (85.1 ± 47.4) %] than that of Sandimmum Neoral, CSS-SM-T displayed lower fluctuations in CsA plasma concentration and obvious sustained-release characteristics in vivo, implying lower toxicity. Therefore, CSS-SM-T provides a new research idea for the design and development of oral sustained- and controlled-release preparations of poorly water-soluble drugs.

Preparation and Formula Optimization of Diphenidol Hydrochloride Push-pull Osmotic Pump Tablets / 中国药师

Objective: To prepare diphenidol hydrochloride push-pull osmotic pump tablets and in-vestigate the influence of differ-ent factors on in-vitro drug release. Methods: The cumulative release of different formulas was detected. Using the cumulative release and similarity factor f2as the evaluation criterion, single factor experiment was applied to screen the core formula and coating process. Results: The drug release behavior was affected by the content of PEO in the drug containing layer, the content of NaCl and the weight gain of the coating layer. After the formula was optimized, the NaCl content in the drug containing layer was 10mg, the PEO-N10 con-tent was 15mg. In the push layer, the content of PEO-WSR303 was 60 mg, that of NaCl was 20 mg. The optimized coating liquid for-mula contained 1. 25 g·L-1PEG4000 and the coating weight gain was 7% of the core. The optimized formula fitted a zero-order equa-tion within 2-12h with the drug release equation of Q=6. 308t-2. 5037(r=0. 995 8). Conclusion: The preparation technology of di-phenidol hydrochloride push-pull osmotic pump tablets is stable, and the in-vitro drug release fits zero-order model.

Formula Optimization of Captopril Timing Osmotic Pump Tablets / 中国药房

OBJECTIVE:To optimize the formula of Captopril timing osmotic pump tablets. METHODS:Using accumulative release rate (Q) as index, single factor test was used to investigate the effects of blocking layer coating weight gain, semipermeable membrane coating weight gain,the type of polyepoxide (PEO),the amount of PEO (3 × 105) and HPMC in drug bearing layer,the amount of PEO (7 × 106) and NaCl in booster layer on drug release of Captopril timing osmotic pump tablets. Based on single factor investigation,using comprehensive score of release behavior(L)as index,the amount of PEO(3×105)and HPMC in drug bearing layer,the amount of PEO(7×106)and NaCl in booster layer as factors,L9(43)orthogonal test was used to optimize the formula of tablet core validation test was conducted. RESULTS:The optimal formula of tablet core included PEO(3× 105)71 mg and HPMC 15 mg in drug bearing layer,PEO(7×106)61 mg and NaCl 18 mg in booster layer,coating weight gain 7％ and semipermeable membrane coating weight gain 10％ in blocking layer. The osmotic pump tablet prepared by optimized formula released after 4 h;in vitro drug release regression equation was Q=5.118t-21.441(R2=0.9956),which was in line with zero-order release characteristics. CONCLUSIONS:The optimal formula is stable,feasible and controllable in quality,and can provide reference for further development of Captopril timing osmotic pump tablets.

Study on Preparation of Methylphenidate Hydrochloride Bipolar Controlled Release Osmotic Pump Tablets / 中国药师

Objective: To study the preparation method and process optimization of methylphenidate hydrochloride biphasic controlled-release osmotic pump tablets.Methods: Based on the preparation technology of double-layer osmotic pump slow-release tablets and combined with the principle of biphasic drug release behavior, the two-release preparation with two different release phases was prepared.Through the single-factor investigation of the drug-containing layer and the booster layer, the amount of the auxiliary materials was determined.The optimum compression method and the optimum coating parameters were obtained by studying the process parameters of tabletting and coating.Results: The prepared methylphenidate biphasic controlled-release osmotic pump tablets had two different release phases.The methylphenidate hydrochloride controlled-release osmotic pump tablets produced by the optimal formulat were good in appearance and reproducibility of drug content.In vitro release curves showed that the drug was released rapidly in the intial 0-2 hour time interval and was in line with zero-order release in 2-10 hour with good reproducibility.Conclusion: The preparation method is scientific, simple and complete, and can be used for preparation of methylphenidate hydrochloride biphasic controlled-release osmotic pump tablets.

Preparation of Double-layer Osmotic Pump Controlled Release Tablets of Fenofibrate-starch Source Mesoporous Carbon Carrier Solid Dispersion / 中国药学杂志

OBJECTIVE: To improve the dissolution rate of fenofibrate (FNB) by using starch source mesoporous carbon (SMC) as a carrier and achieve controlled release of the drug by utilizing double-layer osmotic pump technology to improve the oral bioavailability. METHODS: FNB was loaded into the mesoporous of NMS by adsorption method to prepare the drug loading system (FNB-SMC). Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXDR) were used to characterize the present state of the drug before and after being loaded. The dissolution rate of FNB-SMC was investigated by in vitro dissolution test, and the formulation of the double-layer osmotic pump tablets of FNB-SMC was optimized. The oral bioavailability of the self-made tablet was investigated by in vivo experiment in rabbits. RESULTS: FNB existed in the mesoporous of SMC in an amorphous state. The in vitro dissolution test showed that NMS could significantly increase the dissolution rate of FNB, and the double-layer osmotic pump technology could achieve Zero-order release of the drug. The in vivo experiments showed that the oral bioavailability of the self-made tablets was significantly improved. CONCLUSION: The combination of starch source mesoporous carbon carrier and double-layer osmotic pump technology prevente the burst effect and significantly improve the oral absorption of FNB.

Preparation of micronized nimodipine push-pull osmotic pump tablets / 药学实践杂志

Objective To prepare micronized nimodipine push-pull osmotic pump (PPOP) controlled release tablets . Methods The nimodipine as a model drug ,micronization technique was applied to the PPOP method .Designed and prepared the controlled release of the nimodipine tablet for 12 hours in vitro .The factor f2 was used to evaluate the similarities of differ-ent dissolution profiles ,and the optimal formulation was performed .Results The micronized nimodipine PPOP controlled re-lease tablets were successfully prepared with excellent zero-order release characteristics .The PPOP tablet′s release behavior was close to the zero-order release equation (r= 0 .998 4) .Conclusions The controlled-release formulation was prepared suc-cessfully .Micronized technique combined with the PPOP method significantly increased the release of the nimodipine tablet , the poorly soluble drug ,in vitro .

Preparation and in vitro Release Study of Diphenidol Hydrochloride Double-layer Osmotic Pump Tablets / 中国药房

OBJECTIVE:To prepare Diphenidol hydrochloride double-layer osmotic pump tablets,and study its in vitro release characteristics. METHODS:Double-layer compressing technique and film coating technology were conducted to prepare Diphenidol hydrochloride double-layer osmotic pump tablets. The in vitro releases of it,Difenidol hydrochloride tablets in market,self-made Difenidol hydrochloride single-layer osmotic pump tablets were compared. RESULTS:The formulation was as follow as diphenidol hydrochloride 75 mg,sodium chloride 10 mg,low-molecular-weight polyoxyethylene 15 mg and right amounts of 5% PVP K30 ethanol solution. Booster layer was high-molecular-weight polyoxyethylene 60 mg,sodium chloride 20 mg,PVP K306 mg,right amounts of magnesium stearate. 12 h cumulative release(Q)of prepared double-layer osmotic pump tablets reached 80%,and the release was in line with zero-order kinetic equation. Q15 min of Difenidol hydrochloride tablets had reached 90%;Q12 h of Difenidol hy-drochloride single-layer osmotic pump tablets was only 51.14%. CONCLUSIONS:The prepared Difenidol hydrochloride dou-ble-layer osmotic pump tablets have sustained release effect,with more complete drug release within 12 h than single-layer one.

Study on Preparation Technology and in vitro Drug Release Behavior of Baicalin Monolithic Osmotic Pump Tablets / 中国药房

OBJECTIVE:To prepare Baicalin monolithic osmotic pump tablets and investigate its in vitro drug release behavior. METHODS:Using accumulative release rate as evaluation index,baicalin solid dispersion was prepared to improve solubility,sin-gle factor test and orthogonal test were used to optimize preparation technology(the amount of penetrating agent and pore-forming agent,weight gaining of coating film) of monolithic osmotic pump tablets using baicalin solid dispersion as intermediate. Release rate and mechanism of samples prepared by optimized technology were investigated in 3 kinds of release medium (water,0.1 mol/L HCl,simulated gastric fluid). RESULTS:The optimal preparation technology was that penetrating agent sodium chloride was 30 mg;pore-forming agent polyethylene glycol 400 was 20% amount of excipient cellulose acetate;weight gaining of coating film was 2%. RSD of 12 h accumulative release rate was 1.06%(n=3)for 3 batches of Baicalin monolithic osmotic pump tablets pre-pared by optimized technology. 12 h accumulative release rate of them in 3 kinds of medium were similar to each other,being all more than 80%. Release equation was in line with zero-order drug release model (r=0.9985). CONCLUSIONS:Prepared Ba-icalin monolithic osmotic pump tablets after optimization can release drug at controlled rate.

Establishment of Drug Release Determination Method for Methylphenidate Hydrochloride Bipolar Con-trolled Release Osmotic Pump Tablets / 中国药师

Objective:To establish the drug release determination conditions and method for methylphenidate hydrochloride bipolar controlled release osmotic pump tablets. Methods: The drug release of the tablets was determined by HPLC using a Diamonsil C18 (250 mm × 4. 6 mm, 5 μm) column with acetonitrile-KH2 PO4 (0. 02 mol·L-1 ,and pH was adjusted to 3. 0 by 1% H3 PO4 solution) (30∶ 70) as the mobile phase at a flow rate of 1 ml·min-1 , the column temperature was 35 ℃ and the injection volume was 20 μl. The effects of release medium, release apparatus and rotation speed on the release of methylphenidate hydrochloride bipolar controlled release osmotic pump tablets were studied as well. Results:The established drug release determination method had a good linear rela-tionship within the range of 1. 0-24. 0 μg·ml-1(r=0. 999 5), and the average recovery was 100. 5%(RSD=1. 58%, n = 6). Un-der the conditions of 900 ml pH 3. 0 phosphate buffer solution as the release medium and the rotation speed of 50 r·min-1 , the drug was quickly released in 0-2h, and then the release behavior was complied with a zero-level model in vitro in 2-10h with the release e-quation of Q=5. 505t+44. 221(r=0. 994 5). Conclusion:The method is simple, accurate and reliable, and suitable for the quality control of methylphenidate hydrochloride bipolar controlled release osmotic pump tablets.

Optimization of prescription of ambroxol hydrochloride sandwich osmotic pump tablets by Box-Behnken design-response surface method / 中国药学杂志

OBJECTIVE: To optimize the formulation of ambroxol hydrochloride sandwich osmotic pump tablets using Box-Behnken design response surface method. METHODS: Firstly, significant factors, including amount of glucose, ratio of pore former to weight of coating, and thicknesss of coating, were chosen carefully by single-factor methods, then Box-Behnken design-response surface method was adopted to understand the effects of these factors on the drug release by using similarity factor f2 as evaluation index. And multiple linear regression model and quadratic polynomial equation were established to evaluate the relationship between these factors and similarity factor f2. Secondly, the permeation mechanism of sandwich osmotic pump was studied carefully by SEM and drug release behavior investigation. RESULTS: The quadratic polynomial equation was ideal to fit the prediction result of drug release; the optimal formulation according to Design-Expert8.0.5 software was established as follows: 50 mg of glucose, 8% of pore former, 9% of coating weight. The f2 was approximate 89.33 compared with ideal drug release curve, which was relatively close to the model-predicted f2 value (88.89). Through investigation of permeation mechanism, it was found that the drug release from this delivery system was driven by osmotic pressure difference between the interior of tablets and the release medium. By means of SEM observation, it was shown that some pores on the coating surface were produced after drug release in the medium, but few before drug release, which cued that a lot of medium got into the interior of tablets through the tunnels formed by the porogen in the coating. CONCLUSION: Box-Behnken design method can be used to optimize the formulation of sandwich osmotic pump tablets.

Preparation and optimization of formulation for lappaconitine hydrobromide push-pull osmotic pump controlled release tablets / 第二军医大学学报

Objective To prepare lappaconitine hydrobromide push-pull osmotic pump controlled release tablets and screen for the optimal formulation. Methods The percent of cumulative release was used as the evaluation index for the drug release profile in vitro. The effects of PEO N750, PEO WSR303, and plasticizer amounts and coating weight gain on the releasing behavior were investigated through single-factor method. Based on single-factor study on the compositions, the optimal formulation for lappaconitine hydrobromide push-pull osmotic pump controlled release tablet was selected via orthogonal design. The in vitro release of the optimized formulation was also fitted to different models. Results The results of orthogonal design indicated that coating weight gain had a significant effect on the drug release in vitro —<0. 05). The optimal formula was as follows; lappaconitine hydrobromide 20 mg, PEO N750 160 mg, NaCl 30 mg in drug layer; PEO WSR303 75 mg, NaCl 20 mg in the push layer; and plasticizer PEG 4000 was 10% and weight gain was 5% in the coating composition The release rate of the tablets with optimized formulation was constant within 12 h, and the cumulative release could reach 95. 02 %. Conclusion The current method to prepare lappaconitine hydrobromide push-pull osmotic pump controlled release tablets is stable, and the in vitro drug release has an excellent zero-release profile within 12 h (r=0. 992 1), which meets the standard for controlled release.