Pharmaceutical Equivalence Research Articles

Sterilization with generic vancomycins of Rattus norvegicus Sprague Dawley hearts from experimental endocarditis by E. faecalis ATCC 29212

The use of generic antibiotics creates suspicion regarding the innovator. In many countries, especially those in the developing world, these drugs are abundant, due to the cost of the innovator acquisition. However, there are many therapeutic failures that doctors report with its use. The objective of this work was to evaluate the efficacy of generic vancomycin, to sterilize the hearts of Rattus norvegicus Sprague Dawley from experimental endocarditis caused with the vancomycin sensitive strain E. faecalis ATCC 29212. Adult male specimens of Rattus norvegicus Sprague-Dawley were used; they were inoculated with the E. faecalis ATCC 29212 strain (1.5 x 108 CFU / ml) intravenously, to produce an experimental endocarditis. The control rat was sacrificed 48 hours after bacterial inoculation. The remaining five rats, also inoculated with E. faecalis ATCC 29212, received the treatment for five days intramuscularly, one rat for each vancomycin under study. Generic vancomycins were from Behrens, Celovan, Fada Pharma, Vancomax, and Vancocyn. To verify the sterility of the hearts with the generic vancomycin, they were placed in BHI broth, at 35°C. Following incubation, E. faecalis ATCC 29212 colony growth was verified and CFUs were counted per gram of cardiac tissue. The control rat had a bacterial growth of 1.8 x 1012 CFU/g of cardiac tissue. The rats treated with Behrens, Vancocyn and Celovan sterilized the hearts, while those treated with Vancomax and Fada Pharma showed bacterial growth (2.8 x 1012 CFU/g and 4.2 x 1010 CFU/g, respectively). In conclusion, the pharmaceutical equivalence of a generic vancomycin, with respect to the innovator, does not guarantee therapeutic equivalence. More studies need to be done on generic antibiotics to ensure their human clinical use.

PHARMACEUTICAL EQUIVALENCE OF METRONIDAZOLE TABLETS USING THE FLOW-THROUGH CELL (USP APPARATUS 4) AND MEDIA OF PHYSIOLOGICAL pH RANGE

Objective: The aim of this work was to evaluate the pharmaceutical equivalence of metronidazole tablets through the study of hydrodynamics of the flow-through cell (USP Apparatus 4) on the dissolution performance of four commercial formulations (500 mg). The results were compared with those found using the USP basket apparatus. Methods: Experiments were performed with 0.1 N hydrochloric acid (pH 1.2), acetate buffer pH 4.5 and phosphate buffer pH 6.8. A USP Apparatus 4 was used with laminar flow at 16 ml/min and 22.6-mm cells. USP basket apparatus was used with 900 ml of each dissolution medium. The dissolution profiles were compared in terms of the mean dissolution time and dissolution efficiency. Results: Significant differences in MDT and DE values of generic formulations vs. reference with both USP apparatuses were found (*P<0.05) hence, dissolution profiles of metronidazole generic formulations cannot be considered similar to the dissolution profile of the reference. After using some equations to explain the release performance of metronidazole, dissolution data were well adjusted to Peppas-Sahlin and logistic models when the flow-through cell was used. Conclusion: The main problem found with the studied formulations was that generic drug products showed different dissolution performances than the reference, and they did not meet the biowaiver criteria for either class I or class III drugs; therefore, they cannot be considered therapeutic equivalents.

Detection of Substandard Medicines in Sudanese Market by Assessing Pharmaceutical Equivalences of Five Brands of Lisinopril 10mg Tablets

AbstractCounterfeit medicines resemble a silent murderer when used to treat life threatening conditions and people of lower-income segment are at greater risk of purchasing and consuming unsafe counterfeit products. The aim of this study is to examine if substandard medicines are circulating in the regulated supply chain of Sudan and to assess the enforcement of law and regulations by drug regulatory authority taking Lisinopril 10mg brands, fully registered in Sudan, as a model drug. The quality of Zestril, P1, P2, P3 and P4 were evaluated by qualifying tablets for harness, friability, disintegration time, dissolution and assay according to pharmacopoeial methods. All brands have passed the official tests, however two of them failed to pass the friability and hardness tests and Zestril failed to pass only the hardness test. The results might be attributed mainly to the variations in excipients used. The formulation that contains only maize starch as binding agent totally failed to pass both hardness and friability tests and was therefore of substandard quality. The studied showed that circulating pharmaceutical alternatives and equivalence in Sudanese market may need more efficient system to assess their quality before and after circulating on the Sudan’s market to safeguard the health of the population.

Biowaiver Study On Three Generic Brands of Amlodipine 10mg Tablets Marketed In Sudan

AbstractAmlodipine besylate is a BCS class I drug used in treatment of hypertension and coronary artery diseases. In this study we determined the bioequivalence of four different brands of amlodipine besylate 10 mg tablets [Norvasc (brand A), Amilodipine (brand B), Amlozal (brand C) and Amlo(brand D)] using Biowaiver, first the pharmaceutical equivalence was evaluated for the four brands using the official standards according to USP pharmacopeia including diameter, hardness, thickness, disintegration, assay and dissolution, then the biowaiver study was done according to WHO guidelines and the dissolution profiles were studied using three different buffer solutions: pH 1.2, 4.5 and 6.8, then the results were evaluated according to specifications of class 1 drugs as Amlodipine is accepted class 1. The four brands complied with requirements of the official tests of diameter, hardness, thickness, disintegration, assay and dissolution. The three brands (B, C and D) were found to be bioequivalent to innovator (Brand A) as they qualify for WHO criteria for Biowaiver (both tests and reference were very rapidly dissolving in the three medias, i.e released more than 85% in 15 minutes), so similarity factor (f2) was not needed to be calculated to evaluate the interchangeability of the four brands.

Quality Control Study of Different Products from Famotidine Tablets in the Iraqi Market

Background: In developing countries, particularly in Iraq, the use of generic medicines has been increasing in recent years, primarily as a cost-saving measure in healthcare provision. In the Iraqi market, famotidine tablets are available from different pharmaceutical companies. As a result, regular pre-marketing quality testing is required to check the quality and identify which product might safely substitute the innovator product in the event of the innovator brand's unavailability or high cost. Objective: various quality control tests have been conducted to determine the Pharmaceutical Equivalence of the different generic and brands of Famotidine film-coated tablets marketed in Iraq. Materials and Methods: Four different samples of the most commonly available Famotidine 20 mg tablets in the Iraqi market were tested for drug contents, friability, and hardness. Additionally, the in-vitro drug release and kinetics were evaluated. Results: slight differences in the products’ content were found; however, they were within the acceptable requirement of British Pharmacopeia (BP) and The United States Pharmacopoeia (USP) 30, NF 25. Similarly, the friability and hardness were within the excellent range according to the B.P. and USP. The results of our study indicated that the tested brand (Famodin) and the three generic products (Famosam, Ulceran, and Famodar) of Famotidine tablets have a unique pattern of in-vitro release profiles. However, all the tested brands and generic pills complied with the USP specifications for the immediate release dosage forms except for Famosam. Release kinetic for the four tested products indicates first-order kinetic models. Conclusion: The findings revealed that nearly all of the tested Famotidine tablet brands and generics met the pharmacopeial requirements for oral tablets. As a result, if acquiring the innovative brand of famotidine tablets is difficult to obtain, healthcare providers may be advised to use the tested products instead.

Influence of Storage Conditions on Pharmaceutical Equivalence and Similarity of Hydrochlorothiazide Tablets in Argentina

Influence of Storage Conditions on Pharmaceutical Equivalence and Similarity of Hydrochlorothiazide Tablets in Argentina

Definition of Multivariate Acceptance Limits (Guard-Bands) Applied to Pharmaceutical Equivalence Assessment

Definition of Multivariate Acceptance Limits (Guard-Bands) Applied to Pharmaceutical Equivalence Assessment

Pharmaceutical equivalence study of marketed ibuprofen tablets of UAE using a validated RP-HPLC method

This study was carried out on the development of the RP-HPLC method and its application in the pharmaceutical equivalence study of ibuprofen tablets that are commercially available in the United Arab Emirates pharmaceutical markets. Three local and six imported brands of ibuprofen tablets were included in this study. The physical parameters of all products were recorded. An RP-HPLC system was developed and validated for the identification and quantification of the ibuprofen present within the tablets. The dissolution study was carried out using both UV-spectrophotometry (United State Pharmacopeia 42-National Formulary-37) and the RP-HPLC method with eight sampling data points. The dissolution profiles of eight test products were compared with a reference product (Switzerland), and similarity/ difference factors were calculated. The developed RP-HPLC method was simple, precise, and suitable for the quantification of ibuprofen present within the tablets. The studied products contained 97.46%–107.58% ibuprofen. The products released about 92.44%–110.63% ibuprofen within 60 minutes except one imported product that released only 12.51% of the drug. Based on similarity factor reference ranges (50%–100%), three products exhibited more than 50% similarity in dissolution profiles. In conclusion, the studied products passed the test for physical parameters, drug contents, and dissolution study except for an imported product. Based on calculated similarity factors, three products were a pharmaceutical equivalent to the reference product in respect to dissolution profiles comparison.

Viscoelastic and Deformation Characteristics of Structurally Different Commercial Topical Systems.

Rheological characteristics and shear response have potential implication in defining the pharmaceutical equivalence, therapeutic equivalence, and perceptive equivalence of commercial topical products. Three creams (C1 and C3 as oil-in-water and C2 as water-in-oil emulsions), and two gels (G1 and G2 carbomer-based) were characterized using the dynamic range of controlled shear in steady-state flow and oscillatory modes. All products, other than C3, met the Critical Quality Attribute criteria for high zero-shear viscosity (η0) of 2.6 × 104 to 1.5 × 105 Pa∙s and yield stress (τ0) of 55 to 277 Pa. C3 exhibited a smaller linear viscoelastic region and lower η0 (2547 Pa∙s) and τ0 (2 Pa), consistent with lotion-like behavior. All dose forms showed viscoelastic solid behavior having a storage modulus (G′) higher than the loss modulus (G″) in the linear viscoelastic region. However, the transition of G′ > G″ to G″ > G′ during the continual strain increment was more rapid for the creams, elucidating a relatively brittle deformation, whereas these transitions in gels were more prolonged, consistent with a gradual disentanglement of the polymer network. In conclusion, these analyses not only ensure quality and stability, but also enable the microstructure to be characterized as being flexible (gels) or inelastic (creams).

EVALUATION OF PHARMACEUTICAL EQUIVALENCE OF VARIOUS LOCAL BRANDS OF METFORMIN HCL TABLETS IN PAKISTAN

Present study aimed to assess pharmaceutical equivalence of five different local brands of Metformin tablets in Pakistan. The brands were treated for different quality attributes according to the BP and USP pharmacopeial and non-pharmacopeial methods. Shelf life was determined by R-Gui software while model independent and dependent approaches were used for in-vitro dissolution profile study. Among all brands, A (2.83) and D (3.5) passed claimed shelf life of 3 years. Moreover, only one out of five brands that is brand A (f2= 53.58 and f1= 5.98) showed equivalence release to innovator (brand C) at each time point in BP mentioned pH 6.8 media, falling in standard range of f2=50-100 and f1=0-15 therefore they are interchangeable (P<0.01). However, the other 3 brands showed insignificant similarity. Present findings supports the need to conduct post-quality evaluation by regulatory authority for locally available pharmaceutical products.

Risk of false pharmaceutical equivalence (non-equivalence) decisions due to measurement uncertainty

The pharmaceutical equivalence between test (generic or similar) and reference medicine is evaluated through in vitro quality tests involving multiple compliance parameters. Despite efforts to ensure the reliability of the analytical results obtained in the pharmaceutical equivalence studies, measurement uncertainties lead to a risk of false decisions. Thus, the aim of this work was to evaluate the measurement uncertainties associated with the analytical results obtained in the pharmaceutical equivalence studies of different pharmaceutical forms and to estimate the risks of false decisions in the evaluation of pharmaceutical equivalence. The measurement uncertainties associated with the test results were evaluated using the bottom-up and top-down approaches. The consumer’s or producer’s combined particular risks and combined total risks were estimated using the Monte Carlo method implemented in MS-Excel spreadsheet (available as supplemental material). Considering the seven pharmaceutical equivalence studies performed in this work, three studies were not conclusive (risk of false pharmaceutical equivalence decisions higher than 5 %). Moreover, we concluded pharmaceutical equivalence and pharmaceutical non-equivalence in one and three studies, respectively. The particular and total combined risks are useful to make decisions regarding the evaluation of pharmaceutical equivalence between the test (generic or similar) and reference medicines. Regulatory bodies and pharmaceutical equivalence centers are very interested in the estimation of the risks of false decisions, particularly to evaluate the quality of medicines that are not submitted to bioequivalence studies.

The Implications of Regulatory Framework for Topical Semisolid Drug Products: From Critical Quality and Performance Attributes towards Establishing Bioequivalence.

Due to complex interdependent relationships affecting their microstructure, topical semisolid drug formulations face unique obstacles to the development of generics compared to other drug products. Traditionally, establishing bioequivalence is based on comparative clinical trials, which are expensive and often associated with high degrees of variability and low sensitivity in detecting formulation differences. To address this issue, leading regulatory agencies have aimed to advance guidelines relevant to topical generics, ultimately accepting different non-clinical, in vitro/in vivo surrogate methods for topical bioequivalence assessment. Unfortunately, according to both industry and academia stakeholders, these efforts are far from flawless, and often upsurge the potential for result variability and a number of other failure modes. This paper offers a comprehensive review of the literature focused on amending regulatory positions concerning the demonstration of (i) extended pharmaceutical equivalence and (ii) equivalence with respect to the efficacy of topical semisolids. The proposed corrective measures are disclosed and critically discussed, as they span from mere demands to widen the acceptance range (e.g., from ±10% to ±20%/±25% for rheology and in vitro release parameters highly prone to batch-to-batch variability) or reassess the optimal number of samples required to reach the desired statistical power, but also rely on specific data modeling or novel statistical approaches.

Assessment of the pharmaceutical equivalence and in vitro dissolution studies of amlodipine tablets marketed in Northern Nigeria

The extensive supply of poor quality and/or counterfeit drug products in many developing countries has made it vital to frequently carry out suitable tests to assess bioequivalence (BE) in a cost-effective manner. This study was intended to assess the pharmaceutical equivalence and dissolution profile of amlodipine 5mg tablets marketed in Jos and Kaduna metropolis. Ten brands of Amlodipine 5mg tablets were obtained from different community pharmacies and evaluated for different quality control parameters such as percent drug content, friability, hardness, thickness, weight uniformity, disintegration time, and dissolution. The results showed that brands F and I failed the test for percent drug content while the rest of the brands passed it. In addition, all the brands passed the disintegrationand friability test while Brands C, F and I did not pass the hardness test. The dissolution profiles of all the brands were similar to the innovator brand at pH 6.8, whereas at pH 1.2, only four brands (B, E, H and I) had similar dissolution profile to the innovator. This study serves to justify for the assessment of in vitro parameters of commercially available amlodipine generics which may aid the prescribers’ decision making.
 Keywords: Amlodipine; Jos; Tablet properties, Dissolution profile

Tackling the challenges of nanomedicines: are we ready?

PurposeThis review provides an overview of the proceedings of the symposium “Tackling the Challenges of Nanomedicines: Are We Ready?” organized by the International Pharmaceutical Federation (FIP) Hospital Pharmacy Section and Non-Biological Complex Drugs (NBCDs) Working Group at the 2019 FIP World Congress of Pharmacy and Pharmaceutical Sciences. Debate centered on reasons underlying the current complex regulatory landscape for nanomedicines and their follow-on products (referred to as nanosimilars) and the pivotal role of hospital pharmacists in selecting, handling, and guiding usage of nanomedicines and nanosimilars.SummaryThe evaluation and use of nanomedicines are recognized among scientific, pharmaceutical, and regulatory bodies as complex. Interchangeability and substitutability of nanomedicines and nanosimilars are confounded by a lack of pharmaceutical and pharmacological equivalence, reflecting the inherent complex nature of these drug products and manufacturing processes. Consequences include implications for clinical safety and efficacy and, ultimately, comparability. Local regulatory approvals of some nanomedicines have occurred, but there is no standard to ensure streamlined evaluation and use of consistent measures of therapeutic equivalence of reference products and their nanosimilars. Hospital pharmacists are expected to be experts in the selection, handling, and substitution of nanomedicines and familiarize themselves with the limitations of current methods of assessing pharmaceutical and clinical equivalence of nanosimilars in order to ensure informed formulary decision-making and eventual patient benefit.ConclusionSupportive guidance for pharmacists focusing on the substitutability and/or interchangeability of nanomedicines and their nanosimilars is needed. Current FIP guidance for pharmacists on therapeutic interchange and substitution should be extended to include nanomedicines and nanosimilars.

Comparative studies of the kinetics of dissolution of medicines on the basis of clopidogrel

Generic medicines occupy dominant positions both in the pharmaceutical market of Ukraine and in industrial production by domestic pharmaceutical enterprises. The use of generic drugs in medical practice is of significant medical and social importance for expanding the accessibility of the general population to essential drugs. In Ukraine, more than twenty generic medicines based on clopidogrel, both foreign and domestic, are registered. All generic drugs containing clopidogrel bisulfate must comply with pharmaceutical bisulfate must comply with pharmaceutical equivalence, the kinetics of release of the active pharmaceutical ingredient using the Dissolution test in vitro, and pharmacokinetic parameters in vivo.
 The aim of the work was to carry out comparative studies of the dissolution kinetics of four samples of generic drugs based on clopidogrel with the dissolution kinetics of the original drug Plavix®, to evaluate the similarity factor of dissolution profiles and to determine the effect of biopharmaceutical factors on the equivalence of generics. Comparative studies of the kinetics of dissolution were carried out by the in vitro method according to the «Dissolution» test using a device with a blade with a
 rotation speed of 50 rpm, a dissolution medium with a pH value of 2.0 in a volume of 900 ml at a temperature of 37 ± 1 °C. The determination of the quantitative content of clopidogrel, which passed into the dissolution medium, was carried out by the method of adsorption spectrophotometry in the ultraviolet region at a wavelength of
 about 240 ± 2 nm. Based on the data obtained, the dissolution profiles of the original drug Plavix® and the studied samples of generic drugs were constructed, the similarity of which was assessed by the value of the similarity factor. According to the research results, it was found that one sample of the generic drug proved its equivalence by the in vitro method to Plavix®, and three other samples of generics had differences in dissolution kinetics in comparison with the original drug. Biopharmaceutical factors were analyzed that could affect the dissolution kinetics of the studied generic drugs, from which the physicochemical characteristics of clopidogrel bisulfate, the qualitative and quantitative composition of excipients and the features of the technological process were determined.
 Thus, on the basis of the comparative studies of the dissolution kinetics of drugs based on clopidogrel, generics were found that did not correspond to the in vitro equivalence according to the Dissolution test to the original drug, which could be due to the influence of a combination of biopharmaceutical factors.

Original and generic drugs: what does the clinician need to know?

In the review article modern approaches to testing and registration of generic drugs are discussed. The article presents the history of the formation of the methodology for testing generic drugs and the current legislation of the Russian Federation. The stages of confirmation of equivalence of original and generic drugs are described: pharmaceutical equivalence, bioequivalence and therapeutic equivalence. The methods of assessing bioequivalence - as the main research in the registration of generic drugs - are discussed in detail. Using the example of the original neuroprotector - Mexidol (ethylmethylhydroxypyridine succinate) and its generics, it is described how legislative acts are implemented in practice. It is concluded that not all generic drugs are interchangeable for the original drug.

Application of microbiological assay to determine the potency of intravenous antibiotics

Demonstration of equivalent amounts of active pharmaceutical ingredient is a basic requirement for intravenous generic drugs prior to administration. Physicochemical methods are often used to determine concentration of antibiotics in biological fluids. However, it does not permit direct quantification of potency of a desired antibiotic. This study demonstrates the application of a microbiological assay to determine the potency and concentration of commercially available pharmaceutical-grade antibiotics used for injections. Concentration-dependent variation of inhibitory effect of four commercial brands of cefuroxime and two of ciprofloxacin were observed against two reference bacteria (Escherichia coli DH5α and Escherichia coli ATCC 8739) on Mueller Hinton agar. Regression analysis was used to assess the in vitro equivalence of generic products sold by different retail companies in Dhaka city. A linear relationship was found between the concentration and response of the bacteria in regression analysis where anti-log of X-intercept and slope showed the concentration and potency, respectively. The study showed excellent results of linearity (r2≥0.89), precision (inter assay variation ≤10% for cefuroxime and ≤20% for ciprofloxacin), accuracy and specificity tests for both types of antibiotics. Pharmaceutical equivalence demonstrated by four cefuroxime and two ciprofloxacin samples showed no significantly distinguishable slopes (P > 0.78 and P > 0.44) and intercepts (P > 0.25 and P > 0.07), respectively. Estimated potency for cefuroxime was 91.1-100.0% and for ciprofloxacin was 68.1-100.0%. Microbiological assay was found to be convenient, rapid, cost-effective, precise and accurate in demonstrating pharmaceutical equivalence of antibiotics in different dosage forms. This technique can be used as an alternative method for testing generic antibiotics prior to their use in animal and human.
 Stamford Journal of Microbiology, Vol.10 (1) 2020: 25-29

Converging Generic Drug Product Development: Bioequivalence Design and Reference Product Selection.

Different regulatory agencies provide criteria for selecting a reference product for bioequivalence (BE) studies. In most cases, the criteria vary from one regulatory agency to another, and, consequently, the generic companies often have to repeat the BE studies comparing the same test product with the reference product purchased from a particular country. In addition to being a cost-intensive exercise, this practice is also unethical. The purpose of this article is to discuss the current policy of major regulatory authorities on the selection of the reference product for pharmaceutical equivalence (PE) and BE studies, the cost implications of such regulatory practices, and to also explore the opportunity to harmonize the reference product selection criteria for reducing repetitive BE studies. The regulatory guidance documents of major jurisdictions are reviewed for similarities and differences in generic product definition, BE study design and conduct, and reference product selection criteria for PE and BE studies. A case study is presented to understand how harmonisation can be achieved and how the economic benefits of this harmonisation cannot be underestimated. Harmonisation in reference product selection criteria can pave the way for a common BE study(s) that would be acceptable to the majority of regulatory agencies, and would not only significantly reduce operating costs but would also minimize the exposure of healthy human beings to drugs.

ESTUDO DE EQUIVALÊNCIA FARMACÊUTICA DE COMPRIMIDOS DE CLORIDRATO DE METFORMINA GENÉRICOS E SIMILARES

A metformina é um hipoglicemiante oral da classe das biguanidas muito utilizado no tratamento de diabetes mellitus tipo 2. Os estudos de equivalência farmacêutica destinam-se à avaliação de alguns parâmetros de qualidade dos medicamentos por meio de análise comparativa entre o(s) medicamento(s) teste e o medicamento de referência. Dessa maneira, o presente trabalho teve como objetivo avaliar a equivalência farmacêutica de comprimidos de duas marcas de medicamento genérico e duas marcas de similar frente ao medicamento referência de cloridrato de metformina 850 mg. Os testes realizados nas amostras foram peso médio, teor de substância ativa, friabilidade, desintegração e dissolução. As amostras testadas foram aprovadas em todos os testes, encontrando-se dentro dos limites preconizados pela farmacopeia brasileira 5ª edição. Assim pode-se afi rmar que todos os medicamentos testados são equivalentes farmacêuticos do medicamento referência.

Formulation Development and Evaluation of Duloxetine Hydrochloride Multi-Particulate Delayed-Release Capsules

Background: Multi-particulate drug delivery systems are mainly oral dosage forms consisting of a multiplicity of small discrete units, each exhibiting some desired characteristics. Duloxetine hydrochloride is acid-labile thus it is formulated as gastro-resistant pellets. Objective: The work aims to develop Delayed-release oral capsules comprising Duloxetine Hcl pellets which is similar in dissolution profile and bioavailability, there by establishing bio equivalence to that of the reference product-Cymbalta®. Methods: The pellets are formulated in a fluidised bed processor, by Wurster process. The finished pellet consists of four different layers, coated over the sugar spheres. The first layer is the drug layer, followed by a barrier layer to separate enteric layer and drug, finally a top layer that acts as a moisture barrier. The pharmaceutical equivalence and stability of finished product to that of the standard was the primary objective during the development of each layer. Thus, in all stages of development, the dissolution and stability were closely monitored and the excipients were optimized based omit. Results: Poor process efficiency, multi-pellet formation and low dissolution of the drug layer are resolved by the addition of HPMC, talc and corn starch respectively. The moisture permeability across the barrier layer was arrested by Opadry® AMB white. 25-30%. 25% coating thickness with Eudragit L-30-D55 provides acid resistance and timely drug release. Finally, a 5% coating with Opadry® AMB again provides complete moisture protection. Conclusion: Developed pharmaceutically equivalent and stable dosage form of Duloxetine Hydrochloride