Prediction of in-vitro dissolution and tablet hardness from optical porosity measurements.

Advanced manufacturing technologies such as continuous processing require fast information on the quality of intermediates and products. Process analytical technologies (PAT) to monitor many critical quality attributes (CQAs) have been developed and successfully implemented in pharmaceutical industry. However, there are some CQAs, which still have to be measured off-line with significant effort due to the lack of suitable PAT sensors. Two prominent examples are the in-vitro dissolution and the tablet hardness. Both are obtained via destructive measurement, and the dissolution is tedious and time-consuming to determine. In this study, these two CQAs were predicted via correlation with the optical porosity of tablets. The optical porosity was measured via a novel combination of gas in scattering media absorption spectroscopy (GASMAS) and photon time of flight spectroscopy (pTOFS) with a SpectraPore instrument. The approach was tested in a continuous tableting line and showed promising results in predicting the amount of drug released after specific dissolution times as well as the tablet hardness. This indicates that the measurement of optical porosity can support control strategies within the real-time release testing (RTRT) concept.

Comparison of diterpenoid contents and dissolution profiles of selected Andrographis paniculata crude and extract capsules.

INTRODUCTION: Andrographis paniculata (AP) has been approved by the Thai government for the treatment of mild cases of COVID-19 patients. Increasing use of AP products requires quality control to ensure efficacy and safety. At present, there is no requirement for dissolution test of AP products in the Thai Herbal Pharmacopoeia (THP). OBJECTIVE: This work aimed to examine the contents and dissolution profiles of active diterpenoids, andrographolide (AP1), 14-deoxy-11,12-didehydroandrographolide (AP3), neoandrographolide (AP4), and 14-deoxyandrographolide (AP6) in AP capsules available in Thai markets. MATERIALS AND METHODS: Four extract products (EXT. A-D) and three crude powder products (CRD. A-C) were tested for contents by using HPLC-DAD. Dissolution profiles of four diterpenoids were investigated in different media (pH 1.2, 4.5, 6.8, and 0.01 N HCl + SLS) with apparatus II (paddle type). RESULTS: The AP1 contents were 1.99%-2.90% w/w for crude capsules and 2.84%-16.27% w/w for extract capsules. In the dissolution test, the dissolution percentages of four diterpenoids from crude capsules were higher than those from extract capsules except EXT. A. AP1 in most extract products (EXT. B, C, D) was dissolved in all dissolution media at a lower percentage than the other three diterpenoids. EXT. A (aqueous extract) was the only extract capsule showing the amounts of all diterpenoids dissolved in all media >80% in 45 min. CONCLUSION: The study demonstrated that AP1 content in AP products complied with the acceptance criteria in the THP (80%-120%), and the weight variation also met the United States Pharmacopeia (USP) requirements. However, different dissolution profiles of AP products may lead to different bioavailability of diterpenoids and further affect their efficacy.

Romanian Wild-Growing Chelidonium majus-An Emerging Approach to a Potential Antimicrobial Engineering Carrier System Based on AuNPs: In Vitro Investigation and Evaluation.

Novel nanotechnology based on herbal products aspires to be a high-performing therapeutic platform. This study reports the development of an original engineering carrier system that jointly combines the pharmacological action of Chelidonium majus and AuNPs, with unique properties that ensure that the limitations imposed by low stability, toxicity, absorption, and targeted and prolonged release can be overcome. The metabolite profile of Romanian wild-grown Chelidonium majus contains a total of seventy-four phytochemicals belonging to eight secondary metabolite categories, including alkaloids, amino acids, phenolic acids, flavonoids, carotenoids, fatty acids, sterols, and miscellaneous others. In this study, various techniques (XRD, FTIR, SEM, DLS, and TG/DTG) were employed to investigate his new carrier system's morpho-structural and thermal properties. In vitro assays were conducted to evaluate the antioxidant potential and release profile. The results indicate 99.9% and 94.4% dissolution at different pH values for the CG-AuNPs carrier system and 93.5% and 85.26% for greater celandine at pH 4 and pH 7, respectively. Additionally, three in vitro antioxidant assays indicated an increase in antioxidant potential (flavonoid content 3.8%; FRAP assay 24.6%; and DPPH 24.4%) of the CG-AuNPs carrier system compared to the herb sample. The collective results reflect the system's promising perspective as a new efficient antimicrobial and anti-inflammatory candidate with versatile applications, ranging from target delivery systems, oral inflammation (periodontitis), and anti-age cosmetics to extending the shelf lives of products in the food industry.

An Innovative Approach to a Potential Neuroprotective Sideritis scardica-Clinoptilolite Phyto-Nanocarrier: In Vitro Investigation and Evaluation.

The cutting-edge field of nanomedicine combines the power of medicinal plants with nanotechnology to create advanced scaffolds that boast improved bioavailability, biodistribution, and controlled release. In an innovative approach to performant herb nanoproducts, Sideritis scardica Griseb and clinoptilolite were used to benefit from the combined action of both components and enhance the phytochemical's bioavailability, controlled intake, and targeted release. A range of analytical methods, such as SEM-EDX, FT-IR, DLS, and XDR, was employed to examine the morpho-structural features of the nanoproducts. Additionally, thermal stability, antioxidant screening, and in vitro release were investigated. Chemical screening of Sideritis scardica Griseb revealed that it contains a total of ninety-one phytoconstituents from ten chemical categories, including terpenoids, flavonoids, amino acids, phenylethanoid glycosides, phenolic acids, fatty acids, iridoids, sterols, nucleosides, and miscellaneous. The study findings suggest the potential applications as a promising aspirant in neurodegenerative strategy.

Development of Quantitative Comparative Approaches to Support Complex Generic Drug Development.

On October 27-28, 2022, the US Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) hosted a virtual public workshop titled "Best Practices for Utilizing Modeling Approaches to Support Generic Product Development." This report summarizes the presentations and panel discussions for a session titled "Development of Quantitative Comparative Approaches to Support Complex Generic Drug Development." This session featured speakers and panelists from both the generic industry and the FDA who described applications of advanced quantitative approaches for generic drug development and regulatory assessment within three main topics of interest: (1) API sameness assessment for complex generics, (2) particle size distribution assessment, and (3) dissolution profile similarity comparison. The key takeaways were that the analysis of complex data poses significant challenges to the application of conventional statistical bioequivalence methods, and there are various opportunities for using data analytics approaches for developing and applying suitable equivalence assessment method.

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.

Initial evaluation of USP apparatus 4 for measuring dissolution profile of man-made vitreous fibers.

We report the successful evaluation of a US Pharmacopeia Apparatus 4 (USP-4) system in measuring the dissolution profiles of man-made vitreous fibers (MMVF)1. Glass and stone wool fibers with different (high- and low-) solubility profiles were tested in closed-loop configuration using a sodium/potassium phosphate buffer solution or an acetate buffer, respectively. Results confirm a need to operate in diluted conditions to avoid silicon saturation in the simulant solution and suppression of fiber dissolution. A clear fiber-to-fiber differentiation with good cell-to-cell reproducibility was achieved. These findings support the continued development of a USP-4 protocol for MMVF in vitro acellular testing.

Comparing the Performance of Raman and Near-Infrared Imaging in the Prediction of the In Vitro Dissolution Profile of Extended-Release Tablets Based on Artificial Neural Networks.

In this work, the performance of two fast chemical imaging techniques, Raman and near-infrared (NIR) imaging is compared by utilizing these methods to predict the rate of drug release from sustained-release tablets. Sustained release is provided by adding hydroxypropyl methylcellulose (HPMC), as its concentration and particle size determine the dissolution rate of the drug. The chemical images were processed using classical least squares; afterwards, a convolutional neural network was applied to extract information regarding the particle size of HPMC. The chemical images were reduced to an average HPMC concentration and a predicted particle size value; these were used as inputs in an artificial neural network with a single hidden layer to predict the dissolution profile of the tablets. Both NIR and Raman imaging yielded accurate predictions. As the instrumentation of NIR imaging allows faster measurements than Raman imaging, this technique is a better candidate for implementing a real-time technique. The introduction of chemical imaging in the routine quality control of pharmaceutical products would profoundly change quality assurance in the pharmaceutical industry.

In vitro comparative quality evaluation of different brands of carbamazepine tablets commercially available in Dessie town, Northeast Ethiopia.

BACKGROUND: Good-quality drugs that fulfill the regulatory parameters and are produced per the current good manufacturing practice (cGMP) standards are very critical for the best therapeutic outcomes. However, the variety of branded drugs circulation in the market often put clinicians and pharmacists in a difficult situation of choice due to the possibility of interchangeability among brands, so we should ascertain the quality of the various brands of drugs, available in the drug market. The purpose of the study was to evaluate the quality and physicochemical equivalence of six brands of carbamazepine tablets that are commercially available in Dessie town, Northeast Ethiopia. METHODS: An experimental study design was used. Six different brands of carbamazepine tablets were purchased from community pharmacies in Dessie town, Northeast Ethiopia, which were selected using simple random sampling methods. Identification, weight variation, friability, hardness, disintegration, dissolution test, and assay for the content of active ingredients were evaluated according to the procedures described in the United States Pharmacopeia (USP) and British Pharmacopeia (BP), and the results were compared with USP and BP standards. The difference (f1) and similarity (f2) factors were calculated to assess in vitro bioequivalence requirements. RESULTS: The identification test results revealed that all samples contained the stated active pharmaceutical ingredients and all brands of carbamazepine tablets complied with the official specification for weight variation, friability, and hardness tests. The percentage concentration of carbamazepine was found in the range of 97.85 to 102.09, which met the USP specification of 92% to 108% of the stated amount. Similarly, all samples fulfilled disintegration time (i.e., ≤ 30 min) except brand CA1 (34.183 min) and dissolution tolerance limits (i.e., Q ≥ 75% at 60 min), which was found in the range of 91.673% -97.124%. The difference factor (f1) values were < 15 and the similarity factor (f2) values were > 50 for all the tested brands of carbamazepine tablets. CONCLUSION: The present study revealed that all brands of carbamazepine 200 mg tablets met the quality control parameters as per pharmacopoeial specifications except the disintegration test of brand CA1, and could be used each brand interchangeably to achieve the desired therapeutic effect.

Drug-Facilitated Crystallization of Spray-Dried CD-MOFs with Tunable Morphology, Porosity, And Dissolution Profile.

Metal-organic frameworks (MOFs) with versatile functionalities have applications in environmental science, sensor separation, catalysis, and drug delivery. In particular, MOFs used in drug delivery should be biodegradable and easy to control. In this study, spray-dried cyclodextrin-based MOFs (CD-MOFs) with tunable crystallinity, porosity, and dissolution properties were fabricated. The spray-drying precursor properties, such as ethanol volume ratio, incubation time, and precursor concentration, were optimized for controlled crystallization. On the basis of the morphology, X-ray diffraction peak intensity, and specific surface areas of the spray-dried CD-MOF products, they were categorized as amorphous, partially crystalline, and highly crystalline. An active pharmaceutical ingredient ketoconazole (KCZ) was introduced into the precursor to prepare KCZ-containing CD-MOFs. The surface areas of these products were greater by 3-fold (292 m2/g) than that of the plain CD-MOF (94.1 m2/g) prepared using the same parameters. The presence of KCZ in the hydrophobic cavity between the two γ-CD molecules was correlated to the CD-MOF crystal growth. Additionally, CD-MOF particles exhibited different dissolution behaviors on the basis of the position of KCZ in the MOF. These spray-dried CD-MOFs with tunable morphology, specific surface area, and dissolution could have potential applications in various fields.

Harmonizing Biopredictive Methodologies Through the Product Quality Research Institute (PQRI) Part I: Biopredictive Dissolution of Ibuprofen and Dipyridamole Tablets.

Assessing in vivo performance to inform formulation selection and development decisions is an important aspect of drug development. Biopredictive dissolution methodologies for oral dosage forms have been developed to understand in vivo performance, assist in formulation development/optimization, and forecast the outcome of bioequivalence studies by combining them with simulation tools to predict plasma profiles in humans. However, unlike compendial dissolution methodologies, the various biopredictive methodologies have not yet been harmonized or standardized. This manuscript presents the initial phases of an effort to develop best practices and move toward standardization of the biopredictive methodologies through the Product Quality Research Institute (PQRI, https://pqri.org ) entitled "The standardization of in vitro predictive dissolution methodologies and in silico bioequivalence study Working Group." This Working Group (WG) is comprised of participants from 10 pharmaceutical companies and academic institutes. The project will be accomplished in a total of five phases including assessing the performance of dissolution protocols designed by the individual WG members, and then building "best practice" protocols based on the initial dissolution profiles. After refining the "best practice" protocols to produce equivalent dissolution profiles, those will be combined with physiologically based biopharmaceutics models (PBBM) to predict plasma profiles. In this manuscript, the first two of the five phases are reported, namely generating biopredictive dissolution profiles for ibuprofen and dipyridamole and using those dissolution profiles with PBBM to match the clinical plasma profiles. Key experimental parameters are identified, and this knowledge will be applied to build the "best practice" protocol in the next phase.

Dissolution Profile Similarity Assessment-Best Practices, Decision Trees and Global Harmonization.

During the write-up of the meeting summary reports from the 2019 dissolution similarity workshop held at the University of Maryland's Center of Excellence in Regulatory Science and Innovation (M-CERSI), several coauthors continued their discussions to develop a "best-practice" document defining the steps required to assess dissolution profiles in support of certain biowaivers and postapproval changes. In previous reports, current challenges related to dissolution profile studies were discussed such that the steps outlined in the two flow charts ("decision trees") presented here can be applied. These decision trees include both recommendations for the use of equivalence procedures between reference and test products as well as application of the dissolution safe space concept. Common approaches towards establishing dissolution safe spaces are described. This paper encourages the preparation of protocols clearly describing why and how testing is performed along with the expected pass/fail criteria prior to generating data on the materials to be evaluated. The target audience of this manuscript includes CMC regulatory scientists, laboratory analysts, as well as statisticians from industry and regulatory health agencies involved in the assessment of product quality via in vitro dissolution testing. Building upon previous publications, this manuscript provides a solution to the current ambiguity related to dissolution profile comparison. The principles outlined in this and previous manuscripts provide a basis for global regulatory alignment in the application of dissolution profile assessment to support manufacturing changes and biowaiver requests.

Quantitative Assessment of the in vivo Dissolution Rate to Establish a Modified IVIVC for Isosorbide Mononitrate Tablets.

A modified in vitro-in vivo correlation (IVIVC) of the oral solid dosage forms has been proposed as a linear correlation between in vitro and in vivo dissolution. Nevertheless, the analysis of in vivo dissolution is limited by the lack of available methods. In this proof-of-concept study, a novel pharmacokinetic (PK) model containing the in vivo dissolution process and its quantification was presented to directly estimate the in vivo dissolution rate constant (kd). The new model was validated with a hypothetical oral solution (kd â†’ +∞). The accuracy of the new method was clarified by comparing with the relatively true value of kd from the literature. Isosorbide mononitrate (ISMN) was used as a model drug to explore the practicability of the novel method. The dissolution capacities of ISMN reference and test tablets were discriminated by an improved in vitro dissolution method. Following the human PK studies, the kd values and corresponding in vivo dissolution profiles of two formulations were obtained using the novel method. Finally, a modified level A IVIVC between in vitro and in vivo dissolution of ISMN tablets was established, which is expected to guide the optimization of the tablet formulation containing ISMN.

Development of a digital twin of a tablet that mimics a real solid dosage form: Differences in the dissolution profile in conventional mini-USP II and a biorelevant colon model.

The performance of colon-targeted solid dosage forms is commonly assessed using standardised pharmacopeial dissolution apparatuses like the USP II or the miniaturised replica, the mini-USP II. However, these fail to replicate the hydrodynamics and shear stresses in the colonic environment, which is crucial for the tablet's drug release process. In this work, computer simulations are used to create a digital twin of a dissolution apparatus and to develop a method to create a digital twin of a tablet that behaves realistically. These models are used to investigate the drug release profiles and shear rates acting on a tablet at different paddle speeds in the mini-USP II and biorelevant colon models to understand how the mini-USP II can be operated to achieve more realistic (i.e., in vivo) hydrodynamic conditions. The behaviour of the tablet and the motility patterns used in the simulations are derived from experimental and in vivo data, respectively, to obtain profound insights into the tablet's disintegration/drug release processes. We recommend an "on-off" operating mode in the mini-USP II to generate shear rate peaks, which would better reflect the in vivo conditions of the human colon instead of constant paddle speed.

Preparation of Losartan Potassium Controlled Release Matrices and In-Vitro Investigation Using Rate Controlling Agents.

Controlled release matrices have predictable drug release kinetics, provide drugs for an extended period of time, and reduce dosing frequency with improved patient compliance as compared with conventional tablet dosage forms. In the current research work, losartan potassium controlled release matrix tablets were fabricated and prepared with rate altering agents; that is, Ethocel grade 100 combined with Carbopol 934PNF. Various drug to polymer ratios were used. HPMC, CMC, and starch were incorporated in some of the matrices by replacing some amount of filler (5%). The direct compression method was adopted for the preparation of matrices. In phosphate buffer (pH 6.8), the dissolution study was conducted by adopting the USP method-I as the specified method. Drug release kinetics was determined and dissolution profiles were also compared with the reference standard. Prolonged release was observed for all matrices, but those with Ethocel 100FP Premium showed more extended release. The co-excipient (HPMC, CMC, and starch) exhibited enhancement in the drug release rates, while all controlled release matrices released the drug by anamolous non-Fickian diffusion mechanism. This combination of polymers (Ethocel grade 100 with Carbopol 934PNF) efficiently extended the drug release rates up to 24 h. It is suggested that these matrix tablets can be given in once a day dosage, which might improve patient compliance, and the polymeric blend of Ethocel grade 100 with Carbopol 934PNF might be used in the development of prolonged release matrices of other water-soluble drugs.

Pharmaceutical quality evaluation of marketed vildagliptin tablets in Bangladesh based on the United States Pharmacopeia specifications.

Continuous monitoring of pharmaceutical products is vital because it matters to human health. Here we aimed to assess the quality parameters of commercially available vildagliptin tablets in Bangladesh. We tested the tablets for the content uniformity, hardness, friability, disintegration, dissolution, and potency. Then, we fitted the dissolution data with kinetic models to investigate the release pattern of the studied brands. Moreover, we applied a mathematical model-independent approach to compare the dissolution profiles of the brands. The interchangeability was determined using difference and similarity factors. Weight variation, friability, and hardness were between 150.35±1.26 to 230.8±1.98 mg, 0 to 0.88%, and 47.3±5.09 to 108.1±1.92 N, respectively. All tablets disintegrated within 0.54±2.85 to 7.69±2.14 min in distilled water. The potency of tablets in 0.1 N HCl and PBS (pH 6.8) were between 97.67±2.58 to 105±0.95% and 99±4.63 to 105±1.65%, respectively. The drug release (%) in 0.1 N HCl and phosphate-buffered saline (PBS) (pH 6.8) after 60 min were between 99.37±1.80 to 111.09±0.64% and 96.59±3.52 to 109.57±0.53%, respectively. All the brands complied with the United States Pharmacopeia (USP) specification for physicochemical properties. Also, we observed the drug release patterns of vildagliptin tablets matched with different kinetic models. We found only one substitutable brand with the standard product regardless of the dissolution medium. In-vitro chemical equivalence is not always consistent with bioequivalence. Therefore, continuous evaluation of marketed products is essential to ensure the desired quality.

Dissolution profile of different brands of low solubility drugs available in the Nigerian and Brazilian pharmaceutical markets / Dissolution profile of different brands of low solubility drugs available in the Nigerian and Brazilian pharmaceutical markets

The purpose of this work was to elaborate a diagnosis of the dissolution test in Africa in comparison with Brazil, evaluating the dissolution profile of low solubility drugs such as albendazole, ibuprofen, furosemide, glibenclamide, hydrochlorothiazide and carvedilol to ascertain their quality. The dissolution profiles were evaluated by utilizing the United States Pharmacopeia (USP). The glibenclamide medicine was evaluated according to the Food and Drug Administration (FDA), while a dissolution method was developed for the carvedilol medicine. A filter selection test for all the drugs showed that cannula is suitable for all, except for carvedilol, which is centrifuged. The various brands of Nigerian and Brazilian medicines tested showed some statistical differences. The suitable conditions that allowed the dissolution of carvedilol to be determined were the USP type II apparatus at 75 rpm containing 900 mL of acetate buffer, pH 4.5. The results of the dissolution test showed that out of the 17 different brands of Brazilian medicines and 17 different products from Nigeria, 94.12% and 58.82% passed respectively

O objetivo deste trabalho foi elaborar um diagnóstico do teste de dissolução na África em comparação ao Brasil, avaliando o perfil de dissolução de medicamentos de baixa solubilidade como albendazol, ibuprofeno, furosemida, glibenclamida, hidroclorotiazida e carvedilol para verificar sua qualidade.Os perfis de dissolução foram avaliados utilizando a Farmacopeia dos Estados Unidos (USP). O medicamento glibenclamida foi avaliado de acordo com a Food and Drug Administration (FDA), enquanto um método de dissolução foi desenvolvido para o medicamento carvedilol.Um teste de seleção de filtro para todos os medicamentos mostrou que a cânula é adequada para todos, exceto para o carvedilol, que é centrifugado. As diversas marcas de medicamentos Nigerianos e Brasileiros testadas apresentaram algumas diferenças estatísticas. As condições adequadas que permitiram a determinação da dissolução do carvedilol foram o aparelho USP tipo II a 75 rpm contendo 900 mL de tampão acetato, pH 4,5. Os resultados do teste de dissolução mostraram que das 17 diferentes marcas de medicamentos brasileiros e 17 diferentes produtos da Nigéria, 94,12% e 58,82% foram aprovados, respectivamente

Use of biorelevant dissolution media in dissolution tests as a predictive method of oral bioavailability

Abstract Dissolution is a key step in the uptake of oral drugs. In order to compare the behaviour of the dissolution of two formulations, the dissolution profile test was used. This assay must be discriminative and should mimic in vivo conditions. Many dissolution media described in pharmacopoeias are not predictive of bioavailability. Due to this, biorelevant media are used as an alternative to solve this problem. The objective of this work is to evaluate the relevance of biorelevant dissolution media to predict in vivo drug dissolution. For this, a bibliographic search was carried out in scientific databases. The search was first performed for articles verifying the physicochemical properties of human gastrointestinal fluids. Subsequently, a comparison was made between the properties of gastrointestinal fluids and those of biorelevant and pharmacopoeial media. Finally, the results of bioequivalence studies and dissolution profile tests in biorelevant media described in the literature were compared. The results revealed that there are a few publications that have analysed some physicochemical properties of gastrointestinal fluids. In addition, high variability was observed for some properties. Regarding the comparison of these properties with pharmacopoeial media and biorelevant media, the analysis showed that the biorelevant media are more similar to gastrointestinal fluids than the pharmacopoeial media. Finally, the in vitro dissolution profile results were similar to the results obtained in vivo. Thus, biorelevant media may be useful for analysing dissolution profiles.

Comparator product issues for biowaiver implementation: the case of Fluconazole

The aim of this work was to assess if the commercially available Fluconazole drug products (Reference, Generic and Similar) would meet the biowaiver criteria from Food and Drug Administration (FDA) and Brazilian Agency for Health Surveillance (ANVISA) agencies. All formulations were evaluated considering the dissolution profile carried out in Simulated Gastric Fluid (SGF) pH 1.2, Acetate Buffer (AB) pH 4.5 and Simulated Intestinal Fluid (SIF) pH 6.8. The results demonstrated that all formulations fulfilled the 85% of drug dissolved at 30 min criterion in SGF pH 1.2. However, in AB pH 4.5 and SIF pH 6.8, some formulations, including the comparator, did not achieve this dissolution percentage. The discrepant dissolution profiles also failed the ƒ2 similarity factor analysis, since none of the formulations showed values between 50 and 100 in the three dissolution media. Comparative dissolution profiles were not similar, considering that the main issues concerning the dissolution were evidenced for the comparator product. Hence, a revision in the regulatory norms in order to establish criteria to switch the comparator could result in an increased application of drugs based on biowaiver criteria