Development of microparticles and microparticulated tablets containing piperine

Abstract Piper nigrum (black pepper) is used in Indian traditional medicine and its main alkaloid, Piperine (PIP), presents antioxidant, antitumor and neuroprotective pharmacological properties. This substance is insoluble in aqueous media and can irritate the gastrointestinal tract. Aiming to avoid these inconvenient characteristics and enable PIP oral administration, this study suggested the PIP microencapsulation through the emulsion-solvent evaporation method and the preparation of microparticulated tablets by direct compression. An UV-spectroscopy method was validated to quantify PIP. Microparticles and microparticulated tablets were successfully obtained and the microparticles exhibited excellent flow. The scanning electron microscopy images showed that PIP microparticles were intact after compression. The in vitro release showed a controlled release of PIP from microparticles and PIP microparticles from tablets in comparison to PIP and PIP tablets. The release profiles of PIP microparticles and the microparticulated tablets were similar. Therefore, tablets containing PIP microparticles are promising multiparticulated dosage forms because a tablet allows microparticles administration and the intact ones promote a controlled release, decreasing its irritating potential on the mucosa.

Optimization of HPLC method using central composite design for estimation of Torsemide and Eplerenone in tablet dosage form

Abstract A simple, precise, accurate and robust high performance liquid chromatographic method has been developed for simultaneous estimation of Torsemide and Eplerenone in tablet dosage form. Design of experiment was applied for multivariate optimization of the experimental conditions of RP-HPLC method. A Central composite design was used to study the response surface methodology and to analyse in detail the effects of these independent factors on responses. Total eleven experiments along with 3 center points were performed. Two factors were selected to design the matrix, one factor is variation in ratio of Acetonitrile and the second factor is flow rate (mL/min). Optimization in chromatographic conditions was achieved by applying Central composite design. The optimized and predicted data from contour diagram comprised mobile phase (acetonitrile, water and methanol in the ratio of 50: 30: 20 v/v/v respectively), at a flow rate of 1.0 ml/min and at ambient column temperature. Using these optimum conditions baseline separation of both drugs with good resolution and run time of less than 5 minutes were achieved. The optimized assay conditions were validated as per the ICH guidelines (2005). Hence, the results showed that the Quality by design approach could successfully optimize RP-HPLC method for simultaneous estimation of Torsemide and Eplerenone.

Quality control and drug-drug interactions between commercially available Metoprolol and Glimepiride tablets

Abstract Quality is paramount and needs to be maintained throughout the shelf life of pharmaceuticals. The current study aimed to evaluate the quality, potency, and drug-drug interaction in an in vivo animal model by using two drugs, namely, metoprolol and glimepiride. Tablets were selected for their physical characteristics, such as shape, size, and color. Quality control tests, such as weight variation, hardness, friability, and disintegration tests, and invitro drug release studies were performed as per USP. Drug-drug interaction and in vivo studies were carried out according to the standard protocol of the animal ethics committee. Quality control tests of both the tablets were within the specified range. The cumulative release percentages of the drugs were 81.12% and 85.36% for Metoprolol Tartrate and Glimepiride, respectively, in a physiological buffer solution within 1 h. The combination of metoprolol and Glimepiride also significantly decreased the blood glucose level in diabetic animals. However, the blood glucose level increased in the group receiving metoprolol only, but the difference was not significant. The result suggested that the formulations are safe. However, the chronic use of this combination requires frequent monitoring of blood glucose level to improve its efficacy and for the patient's safety.

Stability-indicating capillary zone electrophoresis assay for the analysis of linezolid in tablets

A simple and fast alternative methodology using capillary zone electrophoresis (CZE) to analyze linezolid and its cationic photodegradation products in tablets has been developed. The separation was carried out on fused silica capillary and conducted using 100 mM formic acid (pH 3.0) and by applying 30 KV voltage. Detection was performed at UV 254 nm. The optimized method was validated in terms of linearity, limits of detection and quantification, precision (repeatability), stability studies (selectivity) and accuracy. Good linearity (8-20 mg L-1) was obtained and the limit of detection was 0.95 mg L-1. The greatest advantages of the CZE method were the rapid set-up of instrumentation and capillary equilibration, short analysis time (12 min), low running cost and low waste generation. The method showed good stability in determining linezolid submitted to degradation by light and to a climatic chamber and can be used as an alternative for evaluation in stability studies of linezolid in tablets, as well as for the analysis of the drug in raw materials and finished products.

Pharmacokinetics and safety of repirinast tablets in healthy Chinese subjects

ABSTRACT Repirinast is a new, synthetic, disodium cromoglycate-like antiallergic agent for oral administration in humans. This study evaluated the safety, tolerability and pharmacokinetics of repirinast tablets in healthy Chinese volunteers. This was a phase I, open-label, randomized, single- and multiple-dose study. Subjects were assigned to receive a single dose of repirinast tablet at either 150, 300, or 450 mg, or multiple doses of 150 mg twice daily for 5 days. Plasma samples were analyzed with LC-MS/MS. Pharmacokinetic parameters of active metabolite MY-1250 (deesterified repirinast) were calculated using non-compartmental analysis with WinNonlin software. Statistical analysis was performed using SPSS software. All adverse events (AEs) were mild and of limited duration. No serious adverse event (SAE), death or withdrawal from the study was observed. In the single-dose study, Cmax was reached at about 0.75 hour, and the mean t1/2 was approximately 16.21 hours. Area under curve (AUC) and Cmax increased with dose escalation, but dose proportionality was not observed over the range of 150 to 450 mg. In the multiple-dose study, the steady-state was reached within 3 days with no accumulation. Repirinast tablet was well tolerated in healthy Chinese subjects.

Desenvolvimento de comprimidos de liberação prolongada de nimesulida contendo ferrita para avaliação do trânsito gastrintestinal por meio de técnica biomagnética / Development of prolonged release tablets of nimesulide containing ferrite for evaluation of gastrointestinal transit by means of biomagnetic technique

As Formas Farmacêuticas de Liberação Prolongada (FFLP) têm sido uma alternativa eficaz na terapia, pois proporcionam maior adesão do paciente ao tratamento em função da redução da frequência de dosagem ao longo do dia, sendo sua principal característica, a modulação da liberação/dissolução do fármaco. Entretanto, esta etapa pode ser influenciada por diferentes fatores, dentre eles: os físico-químicos relacionados ao fármaco; os farmacêuticos, principalmente relacionados aos excipientes empregados e às técnicas de obtenção da forma farmacêutica (FF) e os fisiológicos do trato gastrintestinal (TGI), como por exemplo, o pH dos líquidos do TGI, o tempo de esvaziamento gástrico, a motilidade intestinal, entre outros. Desse modo, a avaliação do trânsito da FF no TGI, após a sua administração, permite uma melhor compreensão dos fatores que podem afetar as etapas de liberação/dissolução do fármaco in vivo. Dentre as técnicas empregadas com esse objetivo, destacam-se: a cintilografia e os métodos biomagnéticos. A Biosusceptometria de Corrente Alternada (BAC) é um método biomagnético que tem se mostrado promissor para este tipo de estudo, por ser não invasivo, portátil, livre de radiação ionizante, e por apresentar acurácia e versatilidade. Diante do exposto, o presente trabalho teve como objetivos, desenvolver e caracterizar sob o aspecto biofarmacotécnico in vitro, um sistema de liberação prolongada contendo nimesulida (fármaco-modelo) e marcador magnético (ferrita), visando obtenção de ferramenta para avaliação do trânsito gastrintestinal por meio de técnica biomagnética. Para isto foram desenvolvidas quatro formulações de comprimidos de liberação prolongada contendo nimesulida, ferrita e diferentes concentrações de hidroxipropilmetilcelulose (HPMC): NF1 (30% HPMC); NF2 (23% HPMC); NF3 (17% HPMC) e NF4 (10% HPMC). Essas foram avaliadas quanto ao comportamento de dissolução por meio de ensaios com aparato 4 e avaliação da cinética e da eficiência de dissolução (ED%). Posteriormente, estudos biomagnéticos, in vitro e in vivo, foram conduzidos com emprego da técnica de BAC para a formulação selecionada. Os resultados obtidos mostraram que as 04 formulações desenvolvidas apresentaram porcentagens de dissolução distintas em função das diferentes concentrações de HPMC (NF1 = 13,2%; NF2 = 40,1%; NF3 = 72,5% e NF4 = 91,5%). A formulação NF4, com menor concentração de HPMC, foi escolhida para os estudos por meio de BAC em função dos resultados de ED% (54,3%) e por apresentar comportamento mais próximo de uma formulação de liberação prolongada. Em relação aos resultados de BAC in vitro, destaca-se que a formulação NF4 (10%HPMC) apresentou aumento de área magnética de forma independente do pH do meio, sugerindo que a hidratação/intumescimento da HPMC independe do pH. Em relação à avaliação do trânsito intestinal (estudo in vivo) foram obtidos os seguintes dados: Tempo médio de Residência Gástrica (TTR) - 89 minutos; Tempo médio do Trânsito Orocecal (TTO) - 313 minutos e Tempo médio do Trânsito Intestinal (TTI) - 224 minutos. Os dados de BAC in vivo permitiram observar que o aumento de área magnética atingiu um platô em cerca de 80 minutos após a administração da formulação NF4. A comparação dos dados de BAC in vitro e BAC in vivo, relacionados ao trânsito gastrintestinal, indica que a formulação NF4, após apresentar o ápice de intumescimento, foi capaz de manter sua estrutura permanente ao longo do TGI, favorecendo assim a liberação modulada do fármaco. Os resultados obtidos demonstraram que a formulação desenvolvida foi eficiente para avaliar e caracterizar o trânsito no TGI por meio da técnica de BAC e também permitiram uma estimativa do comportamento do fármaco em relação a solubilidade em cada porção do TGI, proporcionando assim uma ferramenta adequada para avaliação do trânsito do TGI e desenvolvimento de FFLP

Extended Release (ER) dosage forms have been an effective alternative in therapy, since they provide greater patient adherence to treatment as a function of the reduction of the frequency of dosing throughout the day, its main characteristic being the release / dissolution modulation of the drug. However, this stage can be influenced by different factors, among them: the physical and chemical related to the drug; the pharmacists, mainly related to the excipients employed and the techniques of obtaining the form dosage and the physiological ones of the gastrointestinal tract (GI tract), as for example, the pH of the liquid of the GI tract, gastric emptying time, intestinal motility, among others. Thus, assessment of dosage forms transit in GI tract after its administration allows a better understanding of the factors that may affect the drug release / dissolution steps in vivo. Among the techniques used for this purpose, the following stand out: scintigraphy and biomagnetic methods. Alternating Current Biosensiometry (ACB) is a biomagnetic method that has shown promise for this type of study, since it is non-invasive, portable, free of ionizing radiation, and because of its accuracy and versatility. In view of the above, the aim of this work was to develop and characterize a sustained release system containing nimesulide (study drug) and magnetic marker (ferrite) under the in vitro biopharmaceutical aspect, aiming to obtain a tool to evaluate the GI tract transit through means of biomagnetic technique. For this, four formulations of extended release tablets containing nimesulide, ferrite and different concentrations of hydroxypropylmethylcellulose (HPMC): NF1 (30% HPMC) were developed; NF2 (23% HPMC); NF3 (17% HPMC) and NF4 (10% HPMC). These were evaluated for dissolution behavior by apparatus 4, assays and kinetics and dissolution efficiency (ED%). Subsequently, biomagnetic studies, in vitro and in vivo, were conducted using the ACB technique for the selected formulation. The results showed that the formulations developed showed different percentages of dissolution as a function of the different concentrations of HPMC (NF1 = 13.2%, NF2 = 40.1%, NF3 = 72.5% and NF4 = 91.5%). The NF4 formulation, with a lower concentration of HPMC, was chosen for the ACB studies as a function of ED% results (54,3%) and because of the behavior of a sustained release formulation. In relation to the in vitro ACB results, the NF4 formulation (10% HPMC) showed an increase in magnetic area independently of the pH of the medium, suggesting that the HPMC hydration / swelling is independent of pH. In relation to intestinal transit evaluation (in vivo study) the following data were obtained: Mean Time of Gastric Residency (TTR) - 89 minutes; Mean Time of Orocecal Transit (OCTT) - 313 minutes and Mean Time of lntestinal Transit (TTI) - 224 minutes. ACB data in vivo showed that the increase in magnetic area reached a plateau in about 80 minutes after administration of the NF4 formulation. Comparison of in vitro ACB and ACB data in vivo, related to gastrointestinal transit, indicates that the NF4 formulation, after showing the swelling apex, was able to maintain its permanent structure throughout the GI tract, thus favoring the modulated release of the drug. The obtained results demonstrated that the developed formulation was efficient to evaluate and characterize the transit in the GI tract by means of the ACB technique and allowed a prediction of the behavior of the drug in relation to the solubility in each portion of the GI tract, thus providing a suitable tool for evaluation of the GI tract transit and the development of sustained release formulation

Solubility and dissolution enhancement of flurbiprofen by solid dispersion using hydrophilic carriers

ABSTRACT The intent of the current work is to study the effect of polyethylene glycol 8000 and polyethylene glycol 10000 as hydrophilic carriers on dissolution behaviour of flurbiprofen. In the present study, solvent evaporation method was used to prepare flurbiprofen solid dispersions and evaluated for physico-chemical properties, drug-carrier compatibility studies and dissolution behaviour of drug. Solubility studies showed more solubility in higher pH values and formulations SD4 and SD8 were selected to prepare the fast dissolving tablets. FTIR and DSC study showed no interaction and drug was dispersed molecularly in hydrophilic carrier. XRD studies revealed that there was change in the crystallinity of the drug. The results of In vitro studies showed SD8 formulation confer significant improvement (p<0.05) in drug release, Q20 was 99.08±1.35% compared to conventional and marketed tablets (47.31±0.74% and 56.86±1.91%). The mean dissolution time (MDT) was reduced to 8.79 min compared to conventional and marketed tablets (25.76 and 22.22 min.) indicating faster drug release. The DE (% dissolution efficiency) was increased by 2.5 folds (61.63%) compared to conventional tablets (23.71%). From the results, it is evident that polyethylene glycol solid dispersions in less carrier ratio may enhance the solubility and there by improve the dissolution rate of flurbiprofen.

Classification of drug tablets using hyperspectral imaging and wavelength selection with a GAWLS method modified for classification.

Right drug tablets must be brought to the right places. We apply hyperspectral imaging, which can measure infrared spectra at many points on a two-dimensional plane, to classify tablets correctly. The k-nearest neighbor algorithm (kNN) is employed to classify tablets using a database including their spectra and true classes. Although classification accuracy is not 100%, we can correctly classify tablets overall, since spectra at many points are measured with spectroscopy and misclassification at some points does not have much influence on the final tablet classification result. In addition, we propose a wavelength selection method for classification. Genetic algorithm-based wavelength selection is applied to classification and combined with kNN, and thus, not wavelengths but wavelength-regions can be selected in classification problems. Through a case study, we confirmed that the proposed method could classify three kinds of tablets correctly and select appropriate wavelength-regions.

[Application of multicomponent dissolution evaluation method of biopharmaceutics classification system of Chinese materia medica in gegen qinlian tablets].

The study is a paticular embodiment of Chinese patent medicine based on biopharmaceutics classification system of Chinese materia medica (CMMBCS) , focusing on assessment of synchronization issues of dissolution that may affect the timing of the multicomponent absorption. The accumulative dissolution percentages of nine components in Gengen Qinlian tablets in different dissolution solvents and times were determined by HPLC. The dissolution curve was drew and its similarity was evaluated by similarity factors (f2) and cluster method. Results in this experiment showed that the components that peak 7 and peak 8 (baicalin) represented had poor similarity with the reference peak 2 (puerarin). Their similarity factors were both 43 in water dissolution media and 31 and 45 in pH 7.4 dissolution media, respectively. Components that peaks represented had better similarity with the reference peak 2 (puerarin) in other medium. It illustrated that components that peak 3,4,5,6 (berberine) represented had fully synchronous dissolution characteristics with the reference peak 2 (puerarin), components peak 1 and 9 represented had nearly fully synchronous dissolution characteristics with the reference peak 2 (puerarin), while components that peak 7 and 8 (baicalin) represented had no synchronous dissolution characteristics with the reference peak 2 (puerarin).

A suppository-base-matrix tablet for time-dependent colon-specific delivery system

Our research has focused on the main design features and release performances of time-dependent colon-specific (TDCS) delivery tablets, which relies on the relative constancy that is observed in the small intestinal transit time of dosage forms. But inflammatory bowel disease（IBD）can affect the transit time, and usually results in watery stool. Compared to the TDCS and wax-matrix TDCS tablet, a promising time-dependent colon-specific delivery system was investigated. In our study, a suppository-base-matrix coated tablet was evaluated. Water soluble suppository-base helps the expansion of tablet, facilitates uniform film dissolution and achives high osmotic pressure. Combining the expansion of carboxymethyl starch sodium (CMS-Na) and the moisture absorption of NaCl, the coated TDCS tablet obtained a burst and targeted drug delivery system. A very good correlation between in vitro drug release and in vivo outcome was observed. This TDCS coated tablet provides a promising strategy to control drug release to the desired lower gastrointestinal region.

Nossa pesquisa focou-se nas principais características de planejamento e de desempenho de liberação cólon-específica tempo-dependente (TDCS) de comprimidos, que leva em conta a constância relativa observada no tempo de trânsito intestinal das formas de dosagem. A doença inflamatória do intestino (IBD) pode afetar o tempo de trânsito e, geralmente, resulta em fezes aquosas. Comparando ao TDCS e a comprimidos TDCS com matriz-cerosa, investigou-se sistema promissor de liberação cólon-específica tempo-dependente. Em nosso estudo, avaliou-se comprimido revestido com matriz base de supositório. A base de supositório solúvel em água auxilia a expansão do comprimido, facilita a dissolução uniforme do filme e atinge alta pressão osmótica. Associando a expansão do carboximetil amido sódico (CMS-Na) à absorção de umidade do NaCl, o comprimido revestido TDCS originou sistema de liberação direcionado e de erupção. Observou-se correlação muito boa entre a liberação in vitro e a in vivo do fármaco. Este comprimido revestido TDCS representa estratégia promissora para o controle da liberação do fármaco na região gastrintestinal mais baixa.

Simple and rapid spectrophotometric assay of albendazole in pharmaceuticals using iodine and picric acid as CT complexing agents

Two simple, rapid and inexpensive spectrophotometric methods are described for the determination of albendazole (ALB) in bulk drug and in tablets. The methods are based on charge-transfer (CT) complexation reaction involving ALB as n-donor and iodine as σ-acceptor (method A) in dichloromethane or picric acid (PA) as π-acceptor (method B) in chloroform. The absorbance of CT complexes was measured at 380 nm for method A, and 415 nm for method B. The optimization of the experimental conditions is described. Under optimum conditions, Beer's law obeyed over the concentration ranges 8.0-240 and 2.4-42 μg mL-1 for method A and method B, respectively. The apparent molar absorptivity of CT complexes at the respective λmax are calculated to be 1.17×103 and 5.22×103 L mol-1 cm-1 respectively, and the corresponding Sandell sensitivity values are 0.2273 and 0.0509 ng cm-2. The limits of detection (LOD) and quantification (LOQ) are calculated to be (0.69 and 2.08), and (0.10 and 0.30) μg mL-1 with method A, and method B, respectively. The intra-day and inter-day accuracy expressed as % RE and precision expressed as % RSD were less than 3%. The methods were applied to the determination of ALB in tablets.

Dois métodos espectrofotométricos, simples, rápidos e de baixo custo são descritos para a determinação do albendazol (ALB) como fármaco e em comprimidos. Os métodos baseiam-se em reação de complexação de transferência de carga (TC) envolvendo ALB como n-doador e iodo como aceptor de σ (método A) em diclorometano ou ácido pícrico como π-aceptor (método B), em clorofórmio. A absorção de complexos TC foi medida em 380 nm para o método A e 415 nm para o método B. A otimização das condições experimentais é descrita. Sob condições ideais, a lei de Beer é obedecida nas concentrações entre 8,0 e 240 e 2,4 e 42 μg mL-1 para os métodos A e B, respectivamente. A absortividade molar aparente dos complexos de TC no respectivo λ max foi calculada como sendo 1,17×103 e 5,22×103 L mol-1 cm-1, respectivamente, e os valores de sensibilidade de Sandell correspondentes são 0,2273 e 0,0509 ng cm-2. Os limites de detecção (LOD) e quantificação (LOQ) calculados são (0,69 e 2,08) e (0,10 e 0,30) μg mL-1, com o método A e o método B, respectivamente. A exatidão intra-dia e inter-dia, expressa como % de erro relativo e precisão expressa como % DPR foi inferior a 3%. Os métodos foram aplicados para a determinação de ALB em comprimidos.

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

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

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

Comparison of dissolution profile of extended-release oral dosage forms - two one-sided equivalence test

The aim of this work is to present the two one-sided test (TOST) as an alternative approach to compare dissolution profiles of extended-release dosage forms. The dissolution profiles of oxycodone extended-release tablets containing 10 mg, 20 mg and 40 mg (reference and generic) were evaluated according to the requirements described in United States Pharmacopeia. These dissolution profiles were compared using the conventional similarity factor (f2) and the proposed TOST as an equivalence test. TOST is a simple and alternative approach to compare dissolution profiles of extended-release dosage forms. It allows us to identify the time-point (or time-points) that did not show similarity. We concluded that the two one-sided test performed at a significance level of 5% and defined as D = 10 showed results comparable to those obtained by the conventional similarity factor (f2).

O objetivo deste trabalho é apresentar o teste uni-caudal duplo (TOST) como uma abordagem alternativa na comparação do perfil de dissolução de formas farmacêuticas de liberação prolongada. Os perfis de dissolução de comprimidos de liberação prolongada de oxicodona contendo 10 mg, 20 mg e 40 mg (genérico e referência) foram avaliados de acordo com os requisitos descritos na Farmacopeia Americana. Estes perfis de dissolução foram comparados empregando-se o fator de semelhança convencional (f2) e o método TOST como teste de equivalência. TOST é uma abordagem simples e alternativa para a comparação de perfis de dissolução de formas farmacêuticas de liberação prolongada. Este permite identificar o ponto (ou pontos) que não apresentou semelhança. Considerando-se D = 10, concluímos que o teste uni-caudal duplo num nível de significância de 5% apresenta resultados comparáveis àqueles obtidos com o fator de semelhança convencional (f2).

A simple method for the quantification of diclofenac potassium in oral suspension by high-performance liquid chromatography with UV-detection

A rapid, simple and low cost method was developed to determine diclofenac potassium (DP) in oral suspension, using a reverse-phase column (C8, 150 mm x 4.6 mm, 5 µm), mobile phase containing methanol/buffer phosphate (70:30 v/v, pH 2.5), at a flow rate of 1.0 mL/min, isocratic method, and ultraviolet detection at 275 nm. A linear response (r = 1.0000) was observed in the range of 10.0-50.0 µg/mL. Validation parameters such as linearity, specificity, precision, accuracy and robustness were evaluated. The method presented precision (repeatability: relative standard deviation = 1.21% and intermediate precision: between-analyst = 0.85%). The specificity of the assay was evaluated by exposure of diclofenac potassium under conditions of stress such as hydrolysis, photolysis, oxidation and high temperature. The method presented accuracy values between 98.28% and 101.95%. The results demonstrate the validity of the proposed method that allows determination of diclofenac potassium in oral suspension and may be used as an alternative method for routine analysis of this product in quality control.

Desenvolveu-se método simples, de baixo custo para determinar o diclofenaco potássico (DP) em suspensão oral, usando coluna de fase reversa (C8, 150 mm x 4,6 mm, 5 µm), fase móvel contendo metanol/tampão fosfato (70:30 v/v, pH 2,5), com fluxo de 1,0 mL/min, método isocrático e detecção no ultravioleta a 275 nm. Observou-se resposta linear (r = 1,0000) na faixa de 10,0-50,0 µg/mL. Avaliaram-se parâmetros de validação, como linearidade, especificidade, precisão, exatidão e robustez. O método apresentou precisão (repetibilidade: desvio padrão relativo = 1,21% e precisão intermediária: entre analista = 0,85%). A especificidade do ensaio foi avaliada pela exposição do diclofenaco potássico a condições de estresse, tais como hidrólise, fotólise, oxidação e alta temperatura. O método apresentou valores de exatidão entre 98,28% e 101,95%. Os resultados mostram a validade do método proposto, que permite a determinação de diclofenaco potássico em suspensão oral e pode ser utilizado como alternativa para análise de rotina desse produto no controle de qualidade.

Solid dispersion in pharmaceutical technology. Part II. The methods of analysis of solid dispersions and examples of their application.

In the first part of the article solid dispersions were classified the properties and methods of their preparation were described. This section presents methods of analysis of solid dispersions i.e.: thermoanalytical methods, XRPD, FTIR, microscopic methods, dissolution studies and examples of drug forms where solid dispersions were used.

Formulation and evaluation of buccoadhesive quetiapine fumarate tablets

The aim of present study was to develop and evaluate buccoadhesive Quetiapine Fumarate (QF) tablets, which is extensively metabolised by liver. Buccoadhesive tablets of QF were prepared using HPMC K4M, HPMC K15M and combination of carbopol and HPC as mucoadhesive polymers by direct compression method. Sodium deoxycholate was added to formulation to improve the permeation of drug. The formulations were tested for bioadhesion strength, ex vivo residence time, swelling time and in vitro dissolution studies and ex vivo permeation studies. Optimized formulation (F3) showed 92% in vitro release in 8 h and 67% permeation of drug through porcine buccal mucosa and followed fickian release mechanism with zero order kinetics. FTIR studies of optimized formulation showed no evidence of interaction between the drug and polymers. In vivo mucoadhesive behaviour of optimized formulation was performed and subjective parameters were evaluated.

O objetivo do presente estudo foi desenvolver e avaliar os comprimidos bucoadesivos de fumarato de quetiapina (FQ), que é extensivamente metabolizada no fígado. Os comprimidos bucoadesivos de FQ foram preparados utilizando-se HPMC K4M, HPMC K15M e a combinação de carbopol e HPC como polímeros mucoadesivos pelo método de compressão direta. O desoxicolato de sódio foi adicionado à formulação para melhorar a permeação do fármaco. As formulações foram testadas quanto à força de bioadesão, tempo de residência ex vivo, tempo de inchamento, dissolução in vitro e permeação ex vivo. A formulação otimizada (F3) mostrou 92% de liberação in vivo em 8 h e 67% de permeação do fármaco através da mucosa bucal de porco e seguiu o mecanismo fickiano de liberação com cinética de ordem zero. Os estudos de FTIR da formulação otimizada não mostraram evidência da interação entre o fármaco e os polímeros. O comportamento mucoadesivo in vivo da formulação otimizada foi efetuado e avaliaram-se os parâmetros subjetivos.

Development and evaluation of sustained release losartan potassium matrix tablet using kollidon SR as release retardant

The present study was undertaken to develop sustained release (SR) matrix tablets of losartan potassium, an angiotensin-II antagonist for the treatment of hypertension. The tablets were prepared by direct compression method, along with Kollidon SR as release retardant polymer. The amount of losartan potassium remains fixed (100 mg) for all the three formulations whereas the amounts of Kollidon SR were 250 mg, 225 mg, and 200 mg for F-1, F-2, and F-3 respectively. The evaluation involves three stages: the micromeritic properties evaluation of granules, physical property studies of tablets, and in-vitro release kinetics studies. The USP apparatus type II was selected to perform the dissolution test, and the dissolution medium was 900 mL phosphate buffer pH 6.8. The test was carried out at 75 rpm, and the temperature was maintained at 37 ºC ± 0.5 ºC. The release kinetics was analyzed using several kinetics models. Higher polymeric content in the matrix decreased the release rate of drug. At lower polymeric level, the rate and extent of drug release were enhanced. All the formulations followed Higuchi release kinetics where the Regression co-efficient (R²) values are 0.958, 0.944, and 0.920 for F-1, F-2, and F-3 respectively, and they exhibited diffusion dominated drug release. Statistically significant (P<0.05) differences were found among the drug release profile from different level of polymeric matrices. The release mechanism changed from non-fickian (n=0.489 for F-1) to fickian (n=0.439 and 0.429 for F-2, and F-3 respectively) as a function of decreasing the polymer concentration. The Mean Dissolution Time (MDT) values were increased with the increase in polymer concentration.

O presente estudo foi realizado para desenvolver (SR) matriz de comprimidos de liberação sustentada de losartana, um antagonista da angiotensina II, para o tratamento da hipertensão arterial. Os comprimidos foram preparados pelo método de compressão direta com Kollidon SR como polímero de liberação lenta. A quantidade de losartana potássica permanece fixa (100 mg) para todas as três formulações enquanto que as quantidades de Kollidon SR foram de 250 mg, 225 mg e 200 mg para F-1, F-2 e F-3, respectivamente. A avaliação envolve três etapas- propriedades micromeríticas dos grânulos, estudo das propriedades físicas dos comprimidos e estudos de cinética de liberação in vitro.. Selecionoou-se o aparelho USP tipo II para realizar o teste de dissolução em meio com 900 mL de tampão fosfato pH 6,8 . O teste foi realizado em 75 rpm e a temperatura foi mantida a 37 ºC ± 0.5 ºC. Analisou-se a cinética de liberação utilizando-se vários modelos cinéticos. Conteúdo mais alto de polímero na matriz reduziu a taxa de liberação do fármaco. Em níveis mais baixos de polímero, a taxa e a extensão de liberação do fármaco foram aumentados. Todas as formulações seguiram a cinética de liberação de Higuchi, em que os valores do coeficiente de regressão (R2) foram 0,958 , 0,944 e 0,920 para F-1, F-2 e F-3, respectivamente, e elas apresentaram liberação do fármaco dominada pela difusão. Encontraram-se diferenças estatisticamente significativas (P<0,05) entre os perfis de liberação do fármaco com diferentes níveis de matrizes poliméricas. O mecanismo de liberação mudou de não-fickiano(n=0,489 para F-1) para fickiano(n=0,439 e 0,429 para F-2 e F-3, respectivamente) em função da diminuição da concentração de polímero. Os valores do Tempo de Dissolução Média (TDM) aumentaram com o aumento da concentração polímero.

Laser-induced breakdown spectroscopy-based investigation and classification of pharmaceutical tablets using multivariate chemometric analysis.

We report the effectiveness of laser-induced breakdown spectroscopy (LIBS) in probing the content of pharmaceutical tablets and also investigate its feasibility for routine classification. This method is particularly beneficial in applications where its exquisite chemical specificity and suitability for remote and on site characterization significantly improves the speed and accuracy of quality control and assurance process. Our experiments reveal that in addition to the presence of carbon, hydrogen, nitrogen and oxygen, which can be primarily attributed to the active pharmaceutical ingredients, specific inorganic atoms were also present in all the tablets. Initial attempts at classification by a ratiometric approach using oxygen (∼777 nm) to nitrogen (742.36 nm, 744.23 nm and 746.83 nm) compositional values yielded an optimal value at 746.83 nm with the least relative standard deviation but nevertheless failed to provide an acceptable classification. To overcome this bottleneck in the detection process, two chemometric algorithms, i.e. principal component analysis (PCA) and soft independent modeling of class analogy (SIMCA), were implemented to exploit the multivariate nature of the LIBS data demonstrating that LIBS has the potential to differentiate and discriminate among pharmaceutical tablets. We report excellent prospective classification accuracy using supervised classification via the SIMCA algorithm, demonstrating its potential for future applications in process analytical technology, especially for fast on-line process control monitoring applications in the pharmaceutical industry.