Optimization and evaluation of modified release solid dosage forms using artificial neural network.

This study aims to optimize and evaluate drug release kinetics of Modified-Release (MR) solid dosage form of Quetiapine Fumarate MR tablets by using the Artificial Neural Networks (ANNs). In training the neural network, the drug contents of Quetiapine Fumarate MR tablet such as Sodium Citrate, Eudragit® L100 55, Eudragit® L30 D55, Lactose Monohydrate, Dicalcium Phosphate (DCP), and Glyceryl Behenate were used as variable input data and Drug Substance Quetiapine Fumarate, Triethyl Citrate, and Magnesium Stearate were used as constant input data for the formulation of the tablet. The in-vitro dissolution profiles of Quetiapine Fumarate MR tablets at ten different time points were used as a target data. Several layers together build the neural network by connecting the input data with the output data via weights, these weights show importance of input nodes. The training process optimises the weights of the drug product excipients to achieve the desired drug release through the simulation process in MATLAB software. The percentage drug release of predicted formulation matched with the manufactured formulation using the similarity factor (f2), which evaluates network efficiency. The ANNs have enormous potential for rapidly optimizing pharmaceutical formulations with desirable performance characteristics.

Computational quality-by-design strategy to validate high-performance liquid chromatography method for the estimation of meloxicam in bulk dosage forms and milk samples.

Bovine clinical mastitis has significant repercussions for farmers across the globe. Meloxicam, a COX-2 inhibitor, attenuates mastitis symptoms and is also approved for veterinary use. An RP-HPLC (Reverse Phase-High Performance Liquid Chromatography) method development and validation is essential in the pharmaceutical industry to assess API (Active Pharmaceutical Ingredient) quantity present in the pharmaceutical dosage forms. RP-HPLC method of meloxicam was developed and optimized with the aid of QbD (Quality by Design) using Box-Behnken design (BBD). The pH of the aqueous mobile phase, acetonitrile (ACN) percentage, and column temperature were chosen as influence variables, and retention time (RT) and tailing factor (Tf) were selected as response variables. The optimum experimental conditions were selected as pH ~ 3 of the aqueous mobile phase, 65% v/v ACN, and 30˚C as column temperature. The drug was eluted at 6.02 min RT with 1.18 as Tf. The method was subjected to validation for accuracy, linearity, precision, range, sensitivity, and robustness and was found to comply with ICH Q2 (R1) guidelines. The in vitro bioequivalent studies were performed in hydrochloric acid, pH ~ 1.2; acetate buffer, pH ~ 4.5; and phosphate buffer, pH ~ 6.8 for two veterinary brands of meloxicam tablets, and their release profiles were compared by mathematical models. Both the brands, brand 1 and 2 exhibited significant (Unpaired t-test, P < 0.05) differences in dissolution efficiency (DE) and mean dissolution time (MDT) except DE at pH 1.2. However, brands 1 and 2 showed similarity (f2 > 50) in terms of release of meloxicam except at pH 6.8 (f2 = 47.01). The in vitro release of meloxicam followed Peppas kinetics except for brand 2 at pH 6.8, where it followed the Higuchi model. Moreover, the recovery of meloxicam extracted with ACN in the milk sample was estimated to be 99.67 ± 0.58% significantly (Unpaired t-test, P < 0.05) higher than 90.34 ± 6.77% extracted with methanol. In conclusion, the optimized and validated RP-HPLC method of meloxicam may further be used for the analysis of drug content in pharmaceutical dosage forms in addition to biological fluids.

In vitro dissolution profile comparison using bootstrap bias corrected similarity factor, f2.

In vitro dissolution profile has been shown to be correlated with the drug absorption and has often been considered as a metric for assessing in vitro bioequivalence between a test product and corresponding reference one. Various methods have been developed to assess the similarity between two dissolution profiles. In particular, similarity factor f2 has been reviewed and discussed extensively in many statistical articles. Although the f2 lacks inferential statistical properties, the estimation of f2 and its various modified versions were the most widely used metric for comparing dissolution profiles. In this paper, we investigated performances of the naive f2 estimate method, bootstrap f2 confidence interval method and bias corrected-accelerated (BCa) bootstrap f2 confidence interval method for comparing dissolution profiles. Our studies show that naive f2 estimate method and BCa bootstrap f2 confidence interval method are unable to control the type I error rate. The bootstrap f2 confidence interval method can control the type I error rate under a specific level. However, it will cause great conservatism on the power of the test. To solve the potential issues of the previous methods, we recommended a bootstrap bias corrected (BC) f2 confidence interval method in this paper. The type I error rate, power and sensitivity among different f2 methods were compared based on simulations. The recommended bootstrap BC f2 confidence interval method shows better control of type I error than the naive f2 estimate method and BCa bootstrap f2 confidence interval method. It also provides better power than the bootstrap f2 confidence interval method.

Statistical modeling approaches for the comparison of dissolution profiles.

Dissolution studies are a fundamental component of pharmaceutical drug development, yet many studies rely upon the f 1 and f 2 model-independent approach that is not capable of accounting for uncertainty in parameter estimation when comparing dissolution profiles. In this paper, we deal with the issue of uncertainty quantification by proposing several model-dependent approaches for assessing the similarity of two dissolution profiles. We take a statistical modeling approach and allow the dissolution data to be modeled using either a Dirichlet distribution, gamma process model, or Wiener process model. These parametric forms are shown to be reasonable assumptions that are capable of modeling dissolution data well. Furthermore, based on a given statistical model, we are able to use the f 1 difference factor and f 2 similarity factor to test the equivalency of two dissolution profiles via bootstrap confidence intervals. Illustrations highlighting the success of our methods are provided for both Monte Carlo simulation studies, and real dissolution data sets.

Establishment of a discrinatory dissolution method for orlistat capule and evalution of the similarity of dissolution curue / 中国药师

Objective To establish a discriminative dissolution test method for orlistat capsules and evaluate the similarity of dissolution curves of 6 domestic enterprises and imported orlistat capsules.Methods The HPLC method was used,the chromatographic column was Thermo Hyersil GOLD C18(150 mm×4.6 mm,5 μm)column,the mobile phase was acetonitrile and water(85∶15),the flow rate was 1.0 mL·min-1,the detection wavelength was 195 nm,the column temperature was 30℃,and the injection volume was 20 μL.The effects of different concentrations of sodium dodecyl sulfate,different concentrations of sodium chloride and different pH dissolution media on the dissolution curve were investigated,and the best dissolution conditions were selected.The similarity of the dissolution curve was evaluated using the dissolution curve similarity factor method.Results Orlistat had good linear relationship within the range of 5.989-179.697 μg·mL-1(r=0.999 8),and its average recovery rate was 100.4％,with an RSD of 1.1％(n=9).The optimal dissolution conditions selected were as follows:the pH 6.0 phosphate buffer solution containing 1.0％sodium dodecyl sulfate and 0.5％sodium chloride was as dissolution medium;the conduct dissolution tests conducted under conditions of paddle method,75 r·min-1 and medium 1 000 mL.Only one domestic enterprise had a similar dissolution curve between the product and the reference formulation,while the other five enterprises had inconsistent dissolution behavior between the product and the reference formulation.Conclusion This measurement method can effectively distinguish the dissolution behavior of products from different enterprises,and has certain reference significance to evaluate the consistency of the quality and efficacy of orlistat capsules in China.

Development of Simple Dissolution Methods for Felodipine and Combined Amlodipine Besylate-Indapamide Extended Release Tablets without Stationary (Felodipine) Basket.

BACKGROUND: The dissolution method for certain drugs needs specialized conditions. Dissolution testing for felodipine extended release (ER) tablets (Plendil® 5 mg) and amlodipine-indapamide fixed dose (Natrilam®, 5/1.5 mg) ER tablets requires the use of a stationary (felodipine) basket in USP Apparatus II. OBJECTIVE: The study aimed to develop simple methods for Plendil® and Natrilam® without the use of a felodipine basket. METHODS: The dissolution profiles obtained from different media and paddle speeds were used to compute miscellaneous dissolution parameters and were compared to those obtained from standard (existing) methods using a felodipine basket. RESULTS: The f1, f2, and bootstrap f2 (5th % percentile) values for Plendil® 2.47, 88.17, and 54.62, respectively, and all other dissolution factors revealed similarity between standard and the selected test method with 1% Tween 20 at 50 rpm. For Natrilam®, f1 and f2 and bootstrap f2 5.13, 72.92, and 62.67, respectively, and all other dissolution parameters showed similarity of the standard and selected test method using 0.1N HCl media having 0.38 gm/L EDTA with a sinker at 100 rpm. Release of products assumed zero-order and Weibull model, respectively. CONCLUSION: Test dissolution methods for Plendil® and Natrilam® tablets produced equivalent dissolution profiles compared to their respective standard methods with stationary basket USP Apparatus II.

Compression of amorphous solid dispersions prepared by hot-melt extrusion, spray drying and vacuum drum drying.

The present study explored vacuum drum drying (VDD) as an alternative technology for amorphous solid dispersions (ASDs) manufacture compared to hot-melt extrusion (HME) and spray drying (SD) focusing on downstream processability (powder properties, compression behavior and tablet performance). Ritonavir (15% w/w) in a copovidone/sorbitan monolaurate matrix was used as ASD model system. The pure ASDs and respective tablet blends (TB) (addition of filler, glidant, lubricant) were investigated. Milled extrudate showed superior powder properties (e.g., flowability, bulk density) compared to VDD and SD, which could be compensated by the addition of 12.9% outer phase. Advantageously, the VDD intermediate was directly compressible, whereas the SD material was not, resulting in tablets with defects based on a high degree of elastic recovery. Compared to HME, the VDD material showed superior tabletability when formulated as TB, resulting in stronger compacts at even lower solid fraction values. Despite the differences in tablet processing, tablets showed similar tablet performance in terms of disintegration and dissolution independent of the ASD origin. In conclusion, VDD is a valid alternative to manufacture ASDs. VDD offered advantageous downstream processability compared to SD: less solvents and process steps required (no second drying), improved powder properties and suitable for direct compression.

Estimators and confidence intervals of f2 using bootstrap methodology for the comparison of dissolution profiles.

BACKGROUND AND OBJECTIVES: The most widely used method to compare dissolution profiles is the similarity factor f2. When this method is not applicable, the confidence interval of f2 using bootstrap methodology has been recommended instead. As neither details of the estimator nor the types of confidence intervals are described in the guidelines, the suitability of five estimators and fourteen types of confidence intervals were investigated in this study by simulation. METHODS: One million individual dissolution profiles were simulated for the reference and test populations with predefined target population f2 values, where random samples of different sizes were drawn without replacement. From each pair of random samples, five f2 estimators were calculated, and fourteen types of confidence intervals were obtained using 5000 bootstrap samples. The whole process was repeated 10000 times and the percentage of the similarity conclusions was measured. In addition, the uncertainty associated with the current practice of using f^2 point estimate alone for the statistical inference was evaluated. RESULTS: When combined with different types of confidence intervals, the estimated f2 (f^2), the bias-corrected f2 (f^2,bc), and the variance- and bias-corrected f2 (f^2,vcbc) are not suitable estimators due to higher-than-acceptable type I errors. The estimator f^2,exp, calculated based on the mathematical expectation of f^2, and f^2,vcexp, the variance-corrected f^2,exp, showed acceptable type I errors when combined with any of the ten percentile intervals. However, they have the drawback of low power, which might be addressed by increasing the sample size. To properly control the type I error, samples with at least 12 units should be used. CONCLUSION: The best combinations of estimator and type of confidence interval are f^2,exp and f^2,vcexp combined with any of the ten types of percentile intervals. When the sample f2 value is close to 50, the use of the confidence interval of f2 is recommended even when the variability of the dissolution profiles is low and the prerequisites defined in the regulatory guidelines for using the conventional f2 method are fulfilled in order to control the type I error rate.

DoE-Based Design of a Simple but Efficient Preparation Method for a Non-Effervescent Gastro-Retentive Floating Tablet Containing Metformin HCl.

A sustained-release non-effervescent floating matrix tablet was prepared using a simple and efficient direct compression of spray-dried granules containing metformin hydrochloride and cetyl alcohol with hydroxypropyl methylcellulose K15M (HPMC K15M). The design of experiments was employed to explore the optimal composition of the tablet. The similarity factor was employed to evaluate the equivalence in dissolution profiles between the test tablets and Glucophage XR as a reference. Bootstrap analysis was used to eliminate the formulations for which the dissolution profile was potentially inequivalent to that of the reference. The optimized tablet consisting of 150 mg of cetyl alcohol and 17% HPMC K15M showed a dissolution profile comparable with that of the reference with a similarity factor of 52.41, exhibited a floating lag time of less than 3 s in buffer media, remained floating for 24 h, and reduced the tablet weight by about 20% compared to that of the reference. The current study sheds light on the potential use of non-effervescent gastro-retentive extended-release tablets for high-dose drugs using a simple and efficient direct compression method, and as a potential alternative treatment for Glucophage XR. This study also highlights the importance of a systematic approach to formulation optimization and the evaluation of the dissolution profile.

In Vitro Dissolution and in Silico Modeling Shortcuts in Bioequivalence Testing.

PURPOSE: To review in vitro testing and simulation platforms that are in current use to predict in vivo performances of generic products as well as other situations to provide evidence for biowaiver and support drug formulations development. METHODS: Pubmed and Google Scholar databases were used to review published literature over the past 10 years. The terms used were "simulation AND bioequivalence" and "modeling AND bioequivalence" in the title field of databases, followed by screening, and then reviewing. RESULTS: A total of 22 research papers were reviewed. Computer simulation using software such as GastroPlus™, PK-Sim® and SimCyp® find applications in drug modeling. Considering the wide use of optimization for in silico predictions to fit observed data, a careful review of publications is required to validate the reliability of these platforms. For immediate release (IR) drug products belonging to the Biopharmaceutics Classification System (BCS) classes I and III, difference factor (ƒ1) and similarity factor (ƒ2) are calculated from the in vitro dissolution data of drug formulations to support biowaiver; however, this method can be more discriminatory and may not be useful for all dissolution profiles. CONCLUSIONS: Computer simulation platforms need to improve their mechanistic physiologically based pharmacokinetic (PBPK) modeling, and if prospectively validated within a small percentage of error from the observed clinical data, they can be valuable tools in bioequivalence (BE) testing and formulation development.

Process control and in vitro/in vivo evaluation of aripiprazole sustained-release microcrystals for intramuscular injection.

This work describes the preparation of aripiprazole sustained-release microcrystals for intramuscular injection, through recrystallization, drying, wet grinding, and solidification steps, which had a great impact on the product quality. Here, we evaluated the crystal form of the drug in each step by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and fourier transform infrared spectroscopy (FT-IR), demonstrating that there is no change in the crystal form of aripiprazole monohydrate (H1) during grinding and freeze-drying. Microscopy and scanning electron microscopy (SEM) data showed that freeze-drying had no effect on the morphology of milled H1, and thermal gravimetric analysis (TGA) results showed that the freeze-dried formulation had acceptable water content. In particular, in this study, a similarity factor fitting was applied to determine the similarity of the particle size cumulative distribution curve, and the similarity factor value (99.00) showed that there was no change in the particle size distribution before and after freeze-drying. A two-chamber transmembrane method was used to investigate the in vitro release of the aripiprazole sustained-release microcrystal (ALSI) and commercial preparations (Abilify Maintena®). The similarity factor fitting of in vitro release profiles and drug cumulative release curves in vivo yielded similarity factor values of 98.00 and 95.43, respectively, indicating similar in vitro release and in vivo bioavailability of rats between the ALSI and Abilify Maintena®. A single-dose administration could produce long-term effects for a month. For a microcrystalline suspension, in addition to the conventional quality control indicators, the similarity of the cumulative particle size distribution, the in vitro release profile, and the similarity of the drug release percentage in vivo can be used to reflect product quality and process control.

Comparison of Dissolution Profiles: A Statistician's Perspective.

Dissolution profile comparisons are used in the context of postapproval changes where the manufacturer has to demonstrate that the quality of the product is not affected by the change. Around this topic, basic statistical principles are in conflict with widely used interpretations of current guidelines, resulting in time-intensive discussions in pharmaceutical practice. From a statistician's perspective, the following suggestions could improve the situation regarding statistical analysis, inference, and interpretation: (1) A clear definition of the variability criterion for the similarity factor, such as that found in the EMA guideline, would be helpful. (2) Sample size recommendations should be interpreted as minimum, not as maximum, requirements. (3) In case of several batches per reference or test group, pooled comparisons should be performed instead of multiple batch-to-batch comparisons. (4) FDA Guideline recommendations concerning multivariate equivalence procedures for highly variable dissolution profiles are based on the state of statistical knowledge in 1997 and need to be updated. (5) The T2 test for equivalence is an appropriate method for comparing highly variable dissolution profiles. Application of the T2 test for equivalence enables reliable equivalence decisions and satisfies the intention of reaching scientific evidence in decision making. Software implementations of this test are available in R and SAS. The article is a summary of the poster of the same name presented at the DIA FDA Statistics Forum 2016. The poster took the third place in the poster award of the conference.

Comparison of dissolution time profiles: No similarity but where is the difference?

The similarity of the dissolution time profiles is routinely determined by various statistical methods, e.g. by calculating the f2 similarity factor, by calculating the multivariate statistical distance or determining the confidence interval of f2 metrics using the bootstrapping method. If the similarity of the dissolution profiles is not achieved, these methods provide no information about the possible causes of the differences in the final dosage forms. In this article it is shown that after introduction of summary parameters into the disintegration-dissolution model (DDM), such as intrinsic lifetime distribution of particles, saturation state function, drug load of the system and applying population data analysis, differences on the level of intrinsic lifetime distributions of particles of active pharmaceutical ingredient in immediately release formulations are identified. The identification of these differences provides important clues to target development of generic formulations or helps to explain possible differences in the in vivo behavior of products.

A Mechanistic Study to Determine the Structural Similarities Between Artificial Membrane Strat-M™ and Biological Membranes and Its Application to Carry Out Skin Permeation Study of Amphotericin B Nanoformulations.

Type of biological membrane used in skin permeation experiment significantly affects skin permeation and deposition potential of tested formulations. In this study, a comparative study has been carried out to evaluate the potential of a synthetic membrane (Strat-M™) with rat, human, and porcine ear skin to carry out skin permeation study of nanoformulations of a high molecular weight drug, amphotericin B. Results demonstrated that the permeation of this high molecular weight drug through Strat-M™ showed close similitude to human skin. Value of correlation coefficient (R2) of log diffusion between Strat-M™ and human skin was found to be 0.99 which demonstrated the similarities of Strat-M™ membrane to the human skin. In similarity factor analysis, the value of f2 was also found to be 85, which further demonstrated the similarities of Strat-M™ membrane to human skin. Moreover, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Brunauer-Emmett-Teller (BET) analysis of synthetic and biological membranes depicted almost similar morphological features (thickness, pore size, surface morphology, and diameter) of synthetic membrane with human skin. The results of the study demonstrated Strat-M™ as a better alternative to carry out skin permeation experiment due to the consistent results, reproducibility, easy availability, and minimum variability with human skin.

A gamma process modeling approach for the comparison of dissolution profiles.

In this paper, we propose a stochastic gamma process model for assessing the similarity of two dissolution profiles. Based on the proposed stochastic model, we utilize the difference factor and similarity factor to test the similarity of two dissolution profiles based on bootstrap confidence intervals. The performances of the proposed methods are compared with a multivariate test procedure via Monte Carlo simulation studies. The proposed testing methods are shown to be powerful and effectively controlling the error rate. The proposed model provides a simple yet useful alternative parametric statistical model for assessing the similarity of two dissolution profiles. All the methods are illustrated with a numerical example.

[A fast adaptive active contour model based on local gray difference for parotid duct].

OBJECTIVE: To establish a fast adaptive active contour model based on local gray difference for parotid duct image segmentation. METHODS: On the basis of the LBF model, we added the mean difference of the local gray scale inside and outside the contour as the energy term of the driving evolution curve, and the local gray-scale variance difference was used to replaceλ1 and λ2 as the control term of the energy parameter value. Two local similarity factors of different neighborhood sizes were introduced to correct the effects of image gray unevenness and boundary blur to improve the segmentation efficiency. RESULTS: During image segmentation, this algorithm allowed for adaptive adjustment of the evolution direction, velocity and the energy weight of the internal and external regions according to the difference of gray mean and variance between the internal and external regions. This algorithm was also capable of detecting the actual boundary in a complex gradient boundary region, thus enabling the evolution curve to approach the target boundary quickly and accurately. CONCLUSIONS: The proposed algorithm is superior to the existing segmentation algorithms and allows fast and accurate segmentation of the parotid duct with well-preserved image details.

Evaluating bioequivalence of meloxicam tablets: is in-vitro dissolution test overdiscriminating?

OBJECTIVES: The aim of the study was to assess the impact of the differences in dissolution profiles of meloxicam tablets on the in-vivo bioavailability parameters after oral administration. METHODS: Compare in-vitro dissolution testing in the recommended media to evaluate in-vivo bioequivalence outcomes for the Biopharmaceutics Classification System Class II weak acidic drugs. Nine Beagle dogs received a single oral administration of each formulation (7.5 mg) in a three-way crossover design. KEY FINDINGS: The dissolution of meloxicam from both test products showed marked differences with that from the reference tablet in pH 1.0, 4.5 and 6.8 media at 50 or 75 rpm. Both formulations exhibiting slow or fast dissolution were then compared with the reference product for in-vivo bioequivalence study. Both products were bioequivalent with the reference tablet in either extent or rate of oral absorption. It indicated that the dissolution profiles which discriminated between the formulations in vitro did not accurately predict the in-vivo bioequivalence outcomes. CONCLUSIONS: Comparative dissolution profiles using similarity factor (f2 ) in the recommended media should be relaxed to fulfil the requirements for the development, scale-up and postapproval changes to immediate release oral solid dosage forms of meloxicam.

A fast adaptive active contour model based on local gray difference for parotid duct / 南方医科大学学报

OBJECTIVE@#To establish a fast adaptive active contour model based on local gray difference for parotid duct image segmentation.@*METHODS@#On the basis of the LBF model, we added the mean difference of the local gray scale inside and outside the contour as the energy term of the driving evolution curve, and the local gray-scale variance difference was used to replace and as the control term of the energy parameter value. Two local similarity factors of different neighborhood sizes were introduced to correct the effects of image gray unevenness and boundary blur to improve the segmentation efficiency.@*RESULTS@#During image segmentation, this algorithm allowed for adaptive adjustment of the evolution direction, velocity and the energy weight of the internal and external regions according to the difference of gray mean and variance between the internal and external regions. This algorithm was also capable of detecting the actual boundary in a complex gradient boundary region, thus enabling the evolution curve to approach the target boundary quickly and accurately.@*CONCLUSIONS@#The proposed algorithm is superior to the existing segmentation algorithms and allows fast and accurate segmentation of the parotid duct with well-preserved image details.

Determination of the Dissolution Curves of Albendazole Tablets / 中国药学杂志

OBJECTIVE: To establish a determination method of the dissolution curves of albendazole tablets with differentiation ability and investigate the similarity of dissolution curves in vitro between reference preparation and generic preparations.METHODS: Paddle method was adopted with rotation speed of 50 r•min-1 and the dissolution medium volume was 900 mL. The dissolution media were pH 1.2 hydrochloric acid solution and water. The similarity factor (f2) method was used to evaluate the comparability of dissolution curves.RESULTS: The three established dissolution curves had good distinguishing ability. As shown by the similarity factor (f2), the generic preparation from manufacture A was similar to the reference preparation, while those from the manufacture B and C were not similar.CONCLUSION: The study provides the experimental basis for the consistency evaluation of the dissolution curves of abendazole tablets.

Similarity Evaluation of Dissolution Curves of Self-made and Original Telmisartan /Hydrochlorothiazide Tablets by the f2 Factor Method / 中国药学杂志

OBJECTIVE: To explore the similarity of the dissolution curves of self-made and original telmisartan /hydrochlorothiazide tablets and provide basis for the prescription and process screening of self-made preparation and the quality similarity evaluation with original preparation. METHODS: The dissolution curves of telmisartan and hydrochlorothiazide from self-made and original preparations in four different dissolution media were determined using HPLC. The HPLC method was performed on Welch Ultimate XB-C8 column (4.6 mm × 250 mm, 5 μm) with mobile phase A consisting of ammonium dihydrogen phosphate solution (2.0 g ammonium dihydrogen phosphate was dissolved in 1 L water then adjusted to pH 3.0 with phosphoric acid) and mobile phase B consisting of acetonitrile- methanol (50:50) at a flow rate of 1.2 mL•min-1. The detection wavelength was set at 270 nm. The injection volume was 20 μL. Then f2 factor method was used to evaluate the similarity. RESULTS: The dissolution curves of self-made and original preparations of telmisartan /hydrochlorothiazide tablets in different dissolution media showed similarity, with the f2 factor ≥50 or the dissolution rate within 15 min≥85%. CONCLUSION: The dissolution behaviors of self-made and original telmisartan /hydrochlorothiazide tablets are basically similar, which indicates that the prescription and technology of self-made preparation are reasonable and feasible.