Alternatives to titanium dioxide in tablet coating.

Titanium dioxide (TiO2) is one of the most commonly used pharmaceutical excipients. It is widely used as a white pigment in tablet and pellet coatings. However, it has recently been under massive criticism as a number of studies suggest a cancerogenic potential. It can therefore no longer be taken for granted that TiO2 will continue to be universally available for drug products. Finding suitable alternatives is hence of special relevance. In this study, a number of different pigments were coated on tablets and their covering potential analyzed. None of the alternative pigments showed comparable effectiveness and efficiency to TiO2, though the CaCO3/CaHPO4-based coating showed the second-best results. Regarding the ability to protect photosensitive active ingredients, ZnO showed a comparable potential as TiO2, while all other pigments failed. Using the alternative pigments as markers for in-line Raman spectroscopy as a process analytical technology was challenging and led to increased prediction errors. Again, the CaCO3/CaHPO4-based coating was the only of the tested alternatives with satisfying results, while all other pigments led to unacceptably high prediction errors.

Effect of coating excipients on chemical stability of active coated tablets.

The objective of this study was to understand the impact of coating excipients on the chemical stability of active pan coated peliglitazar, which was prone to acid as well as base-catalyzed degradation. Four different coating formulations containing either polyvinyl alcohol (PVA) or hydroxypropyl methylcellulose (HPMC) as a coating polymer and triacetin (glycerol triacetate) or polyethylene glycol (PEG) as a plasticizer/detackifier were used for coating of peliglitazar in a perforated pan coater. Tablets of one-milligram strength were manufactured by suspending the drug in the coating suspension and spray coating onto inert core tablets. The active coated tablets were placed on stability (40 °C/75% RH) in high-density polyethylene (HDPE) bottles in closed condition with desiccants or in open condition. Tablet samples were withdrawn and analyzed for degradants using a stability-indicating HPLC method. The overall stability for the film-forming polymer-plasticizer/detackifier combination showed the rank order: HPMC-triacetin > PVA-triacetin > HPMC-PEG > PVA-PEG. Higher stability of triacetin systems over PEG systems was attributed to lower solubility of peliglitazar in triacetin coating systems. For the same plasticizer/detackifier, higher stability of HPMC over PVA-based formulations was attributed to lower solubility and mobility of peliglitazar in HPMC compared with the PVA-based coating.

Influences of different Fe sources on Fe bioavailability and homeostasis in SD rats.

The purpose of this study was to determine whether the enteric coating process affects growth performance, Fe bioavailability, and gene expression levels that maintain iron balance in the body. The test was divided into the control group, ferrous sulfate group, ferrous fumarate group, ferrous glycine chelate(1:1) (Fe-Gly(1:1)) group, ferrous glycine chelate(2:1) (Fe-Gly(2:1)) group, enteric-coated Fe-Gly(1:1) group, and enteric-coated Fe-Gly(2:1) group. The results showed that the growth performance of the rats in each iron supplement group was no significant difference among them. The results of serum biochemical indicators showed that the antioxidant capacity of the rats in the iron supplement group after enteric coating increased. The iron supplementation effect of Fe-Gly(1:1) and Fe-Gly(2:1) was better than that of ferrous sulfate, and the effect of Fe-Gly(1:1) after enteric coating was enhanced. The expression levels of IRP1 and IRP2 in the genes of enteric-coated Fe-Gly(1:1) and enteric-coated Fe-Gly(2:1) were significantly higher than those of ferrous sulfate. The expression levels of IRP1 and IRP2 in the protein of enteric-coated Fe-Gly(1:1) group were significantly higher than those in the Fe-Gly(1:1) group. The above results show that Fe-Gly can improve the bioavailability and antioxidant capacity of iron and reduce the iron output of feces after enteric coating.

In vitro comparative quality evaluation of different brands of esomeprazole tablets available in selected community pharmacies in Dhaka, Bangladesh.

OBJECTIVE: Esomeprazole is the S-isomer of omeprazole, used to treat gastro esophageal reflux disease. It is one of the widely manufactured and marketed drugs by many pharmaceutical companies in Bangladesh. The aim of the study is to compare the different physical parameters including hardness, friability, diameter, thickness, disintegration time, dissolution test and assay for quality evaluation and characterization of tablets of five different brands of Bangladeshi pharmaceutical company. The specified compendial method was followed for their evaluation test. RESULTS: Esomeprazole Mg tablets are enteric coated tablet, there was no disintegration for any brand occurred in 0.1 N HCl after 2 h and all tablets were disintegrated within 19.93 ± 0.04 to 29.05 ± 0.14 min in phosphate buffer (pH 6.8). Weight variation and Hardness were between 1.01 ± 0.29 to 2.01 ± 0.14% and 5.32 ± 0.06 to 7.12 ± 0.12 kgf respectively. Medicine released after 2 h in 0.1 N HCl were varied from 2.55 ± 0.24 to 4.47 ± 0.31% which was less than 10% and in phosphate buffer (pH 6.8) the percentage of medicine release were between 100.9 and 105.9% after 60 min. In case of assay the results of all brands were between 95.28 ± 0.08 and 99.40 ± 0.11%. The obtained results of all parameters were complied with pharmacopoeial limit. So from this study we can conclude that products of esomeprazole available in Bangladeshi pharmaceutical market meet the quality parameter to satisfy therapeutic efficacy.

Application of statistical process control for spotting compliance to good pharmaceutical practice

ABSTRACT For the release of pharmaceutical products into the drug market; most of the pharmaceutical companies depend on acceptance criteria - that are set internally, regulatory and/or pharmacopeially. However, statistical process control monitoring is underestimated in most quality control in cases; although it is important not only for process stability and efficiency assessment but also for compliance with all appropriate pharmaceutical practices such as good manufacturing practice and good laboratory practice, known collectively as GXP. The current work aims to investigate two tablet inspection characteristics monitored during in-process control viz. tablet average weight and hardness. Both properties were assessed during the compression phase of the tablet and before the coating stage. Data gathering was performed by the Quality Assurance Team and processed by Commercial Statistical Software packages. Screening of collected results of 31 batches of an antibacterial tablet - based on Fluoroquinolone -showed that all the tested lots met the release specifications, although the process mean has been unstable which could be strongly evident in the variable control chart. Accordingly, the two inspected processes were not in the state of control and require strong actions to correct for the non-compliance to GXP. What is not controlled cannot be predicted in the future and thus the capability analysis would be of no value except to show the process capability retrospectively only. Setting the rules for the application of Statistical Process Control (SPC) should be mandated by Regulatory Agencies.

Measurement of the Intertablet Coating Uniformity of a Pharmaceutical Pan Coating Process With Combined Terahertz and Optical Coherence Tomography In-Line Sensing.

We present in-line coating thickness measurements acquired simultaneously using 2 independent sensing modalities: terahertz pulsed imaging (TPI) and optical coherence tomography (OCT). Both techniques are sufficiently fast to resolve the coating thickness of individual pharmaceutical tablets in situ during the film coating operation, and both techniques are direct structural imaging techniques that do not require multivariate calibration. The TPI sensor is suitable to measure coatings greater than 50 µm and can penetrate through thick coatings even in the presence of pigments over a wide range of excipients. Due to the long wavelength, terahertz radiation is not affected by scattering from dust within the coater. In contrast, OCT can resolve coating layers as thin as 20 µm and is capable of measuring the intratablet coating uniformity and the intertablet coating thickness distribution within the coating pan. However, the OCT technique is less robust when it comes to the compatibility with excipients, dust, and potentially the maximum coating thickness that can be resolved. Using a custom-built laboratory scale coating unit, the coating thickness measurements were acquired independently by the TPI and OCT sensors throughout a film coating operation. Results of the in-line TPI and OCT measurements were compared against one another and validated with off-line TPI and weight gain measurements. Compared with other process analytical technology sensors, such as near-infrared and Raman spectroscopy, the TPI and OCT sensors can resolve the intertablet thickness distribution based on sampling a significant fraction of the tablet populations in the process. By combining 2 complementary sensing modalities, it was possible to seamlessly monitor the coating process over the range of film thickness from 20 µm to greater than 250 µm.

HPTLC and RP-HPLC methods for simultaneous determination of Paracetamol and Pamabrom in presence of their potential impurities.

Two chromatgraphic methods were developed for determination of Paracetamol (PCM) and Pamabrom (PAM) in presence of P-aminophenol (PAP) and Theophylline (THEO) as potential impurities of both drugs respectively. First method is HPTLC which depends on separation and quantitation of the studied drugs on aluminum plates pre-coated with silica gel 60 F254 as a stationary phase using chloroform:methanol:ethyl acetate:glacial acetic acid (8:0.8:0.6:0.2, v/v/v/v) as mobile phase followed by densitometric measurement of the bands at 254 nm. Second method is RP-HPLC which comprises separation of the studied drugs on a Phenomenex C8 column by gradient elution using mobile phase consisting of sodium dihydrogen phosphate buffer (0.05 M): methanol:acetonitrile (85:10:5, v/v/v) at a flow rate of 1 mL/min for first 7.5 min and (70:20:10, v/v/v) at a flow rate of 1.5 mL/min for the next 5 min. The proposed methods were successfully applied for determination of the potential impurities of PCM and PAM after resolving them from the pure drugs. The developed methods have been validated and proved to meet the requirements delineated by ICH guidelines with respect to linearity, accuracy, precision, specificity and robustness. The validated methods were successfully applied for determination of the studied drugs in their pharmaceutical formulation. The results were statistically compared to those obtained by the reported RP-HPLC method where no significant difference was found; indicating the ability of proposed methods to be used for routine quality control analysis of these drugs.

An ingestible sensor for measuring medication adherence.

In this paper, we describe the design and performance of the first integrated-circuit microsensor developed for daily ingestion by patients. The ingestible sensor is a device that allows patients, families, and physicians to measure medication ingestion and adherence patterns in real time, relate pharmaceutical compliance to important physiologic metrics, and take appropriate action in response to a patient's adherence pattern and specific health metrics. The design and theory of operation of the device are presented, along with key in-vitro and in-vivo performance results. The chemical, toxicological, mechanical, and electrical safety tests performed to establish the device's safety profile are described in detail. Finally, aggregate results from multiple clinical trials involving 412 patients and 5656 days of system usage are presented to demonstrate the device's reliability and performance as part of an overall digital health feedback system.

Enteric coated HPMC capsules plugged with 5-FU loaded microsponges: a potential approach for treatment of colon cancer

The work was aimed at developing novel enteric coated HPMC capsules (ECHC) plugged with 5 Florouracil (5-FU) loaded Microsponges in combination with calcium pectinate beads. Modified quasi-emulsion solvent diffusion method was used to formulate microsponges based on 32 factorial design and the effects of independent variables (volume of organic solvent and Eudragit RS100 content) on the dependent variables (Particle size, %EE & % CDR) were determined. The optimized microsponges (F4) were characterized by SEM, PXRD, TGA and were plugged along with calcium pectinate beads in HPMC capsules and the HPMC capsules were further coated with enteric polymer Eudragit L 100 (Ed-L100) and/ or Eudrgit S 100 (Ed-S 100) in different proportions. In vitro release study of ECHC was performed in various release media sequentially SGF for 2 h, followed by SIF for the next 6 h and then in SCF (in the presence and absence of pectinase enzyme for further 16 h). Drug release was retarded on coating with EdS-100 in comparison to blend of EdS-100: EdL-100 coating. The percentage of 5-FU released at the end of 24 h from ECHC 3 was 97.83 ± 0.12% in the presence of pectinase whereas in control study it was 40.08 ± 0.02% drug. The optimized formulation was subjected to in vivo Roentgenographic studies in New Zealand white rabbits to analyze the in vivo behavior of the developed colon targeted capsules. Pharmacokinetic studies in New Zealand white rabbits were conducted to determine the extent of systemic exposure provided by the developed formulation in comparison to 5-FU aqueous solutions. Thus, enteric coated HPMC capsules plugged with 5-FU loaded microsponges and calcium pectinate beads proved to be promising dosage form for colon targeted drug delivery to treat colorectal cancer.

O trabalho teve como objetivo o desenvolvimento de novas cápsulas com revestimento entérico HPMC (ECHC) conectadas com microesponjas carregadas com fluoruracila (5-FU) em combinação com grânuos de pectinato de cálcio. O método de difusão de solvente modificado quasi-emulsão foi usado para formular microesponjas com base no planejamento fatorial 32 e determinaram-se os efeitos das variáveis independentes (volume de solvente orgânico e conteúdo Eudragit RS100) sobre as variáveis dependentes (tamanho de partícula, EE% e % CDR). As microesponjas otimizadas (F4) foram caracterizadas por SEM, PXRD, TGA e ligadas aos grânulos de pectinato de cálcio em cápsulas de HPMC e estas foram, ainda, revestidas com polímero entérico Eudragit L 100 (Ed-L100) e/ou Eudrgit S 100 (Ed S 100) em diferentes proporções. No estudo de liberação in vitro de ECHC foi realizada em vários meios de liberação sequencial SGF durante 2 h, seguido de SIF para as próximas 6 h, e, em seguida, em SCF (na presença e na ausência de enzima pectinase por mais 16 h). A liberação do fármaco foi retardada em revestimento com a EDS-100, em comparação com mistura de EDS-100: EDL-100, de revestimento. O percentual de 5-FU liberado de ECHC 3 ao final de 24 h foi 97,83 ± 0,12% em presença de pectinase, enquanto que para o controle foi de 40,08 ± 0,02% do fármaco. A formulação otimizada foi submetida a estudos Roentgenográficos in vivo, em coelhos brancos Nova Zelândia, para analisar o comportamento das cápsulas desenvolvidas direcionadas ao cólon. Os estudos de farmacocinética em coelhos brancos da Nova Zelândia foram conduzidos para determinar a extensão da exposição sistêmica propiciada pela formulação desenvolvida, em comparação com solução aquosa de 5-FU. Assim, cápsulas entéricas de HPMC revestidas e conectadas com microesponjas carregadas com 5-FU e grânulos de pectinato de cálcio se mostraram promissoras como formulação para liberação do fármaco no cólon no tratamento do câncer colorretal.

Rapid profiling of enteric coated drug delivery spheres via broadband acoustic resonance dissolution spectroscopy (BARDS).

There is an increased trend towards the use of drug and enteric coated sugar spheres for controlled oral delivery of active pharmaceutical ingredients (API). This trend is driven by increased efficacy and ease of formulation of different dosage levels. However, difficulties exist in determining the thickness of drug and enteric coatings in a time efficient manner during manufacture, quality assurance and stability testing. The thickness of the coating determines the dosage of the API and the thickness of the enteric coating determines the release rate of the drug in the gastro-intestinal tract. Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS) offers a rapid new approach to characterising the enteric coating thickness and the raw materials used in their manufacture. BARDS applications are based on reproducible changes in the compressibility of a solvent during dissolution which is monitored acoustically due to associated changes in the speed of sound in solution. It is demonstrated how core delivery sugar spheres have unique acoustic spectra attributable to the mean size distribution of the spheres. A steady state acoustic lag time is associated with the disintegration of the enteric coating, in basic solution. This lag time can be manipulated by varying the concentration of the base which affects the rate at which the coating dissolves. It is anticipated that the thickness/loading of the spheres can be estimated from the lag time.

Automated Dissolution for Enteric-Coated Aspirin Tablets: A Case Study for Method Transfer to a RoboDis II.

Dissolution method transfer is a complicated yet common process in the pharmaceutical industry. With increased pharmaceutical product manufacturing and dissolution acceptance requirements, dissolution testing has become one of the most labor-intensive quality control testing methods. There is an increased trend for automation in dissolution testing, particularly for large pharmaceutical companies to reduce variability and increase personnel efficiency. There is no official guideline for dissolution testing method transfer from a manual, semi-automated, to automated dissolution tester. In this study, a manual multipoint dissolution testing procedure for an enteric-coated aspirin tablet was transferred effectively and reproducibly to a fully automated dissolution testing device, RoboDis II. Enteric-coated aspirin samples were used as a model formulation to assess the feasibility and accuracy of media pH change during continuous automated dissolution testing. Several RoboDis II parameters were evaluated to ensure the integrity and equivalency of dissolution method transfer from a manual dissolution tester. This current study provides a systematic outline for the transfer of the manual dissolution testing protocol to an automated dissolution tester. This study further supports that automated dissolution testers compliant with regulatory requirements and similar to manual dissolution testers facilitate method transfer.

Development of a multiparticulate system containing enteric-release mini-tablets of omeprazole

The main aim of this study was to develop a multiparticulate system containing mini-tablets of omeprazole formulated with an enteric polymer with pH-dependent solubility. Pre-formulation studies showed good flow and compaction capacity, leading to the production ofhigh quality mini-tablets. The mini-tablets were coated in a fluidized bed with hydroxypropylmethylcellulose /Eudragit(r) L30D55 and packed into hard gelatin capsules. The dissolution profile showed gastro-resistance and zero-order kinetics. The dissolution profile for the formulation containing lactose as the diluent and coated with 12% (tablet weight gain) of polymer was similar to that ofthe reference drug.

O presente trabalho teve como objetivo desenvolver e avaliar um sistema multiparticulado de liberação modificada, composto por mini-comprimidos revestidos com polímero de liberação pH-dependente, utilizando como fármaco modelo o omeprazol. Os mini-comprimidos (diâmetro de 2,5 mm) foram obtidos em máquina de compresssão excêntrica, revestidos em leito fluidizado com hidroxipropilmetilcelulose/Eudragit(r)L30D55 e, em seguida, acondicionados em cápsulas gelatinosas duras. A partir dos resultados obtidos no perfil de dissolução foi possível demonstrar a liberação gastro-resistente e comportamento cinético de ordem zero. A formulação contendo lactose como diluente, com revestimento de 12% de polímero, demonstrou semelhança com o medicamento referência.

Gastric-resistant isoniazid pellets reduced degradation of rifampicin in acidic medium

Isoniazid and rifampicin are considered the first-line medication for preventing and treating tuberculosis. Rifampicin is degraded in the stomach acidic environment, especially when combined with isoniazid, factor contributing to treatment failure. In this study, gastric-resistant isoniazid pellets were obtained to physical contact of this drug with rifampicin and to bypass the stomach´s acidic environment. The pellets were fabricated using the extrusion-spheronization technique. The coating process was conducted in a fluid spray coater using Acrycoat L 100(r) solution as the coating agent. The pellets obtained were submitted to a dissolution test in HCl 0.1 N and phosphate buffer media. The results indicated that optimum gastric-resistance was only attained with the highest amount of coating material, with isoniazid almost fully released in phosphate buffer. The amount of rifampicin released from its mixture with non-coated isoniazid pellets in HCl 0.1 N was less than that released from its mixture with the enteric-coated pellets. Acrycoat L 100(r) was shown to be an effective enteric/gastric-resistant coating since the stability of rifampicin appeared to be enhanced when physical contact of this drug with isoniazid was prevented at low pH.

Isoniazida e rifampicina são fármacos de primeira escolha para a prevenção e tratamento da tuberculose. A rifampicina degrada-se em condições ácidas do estômago, principalmente na presença da isoniazida, o que contribui para a falha do tratamento. O presente trabalho teve como objetivo a obtenção de péletes de isoniazida gastrorresistentes, visando a evitar contato da rifampicina com isoniazida e consequente degradação no meio ácido estomacal. Os péletes foram produzidos pela técnica de extrusão-esferonização. O processo de revestimento foi conduzido em leito fluidizado com solução orgânica de Acrycoat L 100(r). Os péletes obtidos foram submetidos ao teste de dissolução em HCl 0,1 N e tampão fosfato. Os resultados indicam que a gastrorresistência foi obtida somente com a maior quantidade de revestimento, sendo a isoniazida liberada completamente no meio tampão fosfato. A quantidade de rifampicina dissolvida em meio ácido, quando associada a péletes de isoniazida não revestidos, foi menor do que a observada na presença de péletes de liberação entérica. O polímero Acrycoat L 100(r) mostrou-se eficiente para o recobrimento com a função de gastrorresistência, indicando que a instabilidade da rifampicina pode ser reduzida nas associações com a isoniazida através do revestimento entérico da isoniazida.

Formulation, in vitro drug release and in vivo human X-ray investigation of polysaccharide based drug delivery systems for targeting 5-fluorouracil to the colon

The purpose of this research study was to develop 5-fluorouracil compression coated tablets by using biodegradable polysaccharide polymer locust bean gum (LBG) and hydroxyl propyl methyl cellulose (HPMC) as coating materials. The fast disintegrating core tablets containing 50 mg of 5-fluorouracil were compression coated with LBG and HPMC in different ratios (8:1, 7:2 and 6:3) with a coat weight of 300, 400 and 500 mg. In vitro dissolution data indicated that the formulation (CLH63) with a coat weight of 500 mg containing LBG and HPMC in the ratio 6:3 gave the best release profile (0% in first 5 hour and 96.18% in 24 hours). DSC and FTIR results indicated no possibility of interaction between drug and polymers or other excipients. In vivo human X-ray studies revealed that formulation CLH63 was able to resist breakdown in the stomach and small intestine. The disintegration of the tablet occurred in the colon between 8 to 16 hours of post dose. By the present study, it can be concluded that the LBG and HPMC based compression coated tablets of 5-fluorouracil will be useful strategy for colonic delivery of 5-fluorouracil without being released in upper gastrointestinal region for the safe and effective management of colon cancer.

O propósito desta pesquisa foi desenvolver comprimidos revestidos de fluoruracila utilizando polissacarídio biodegradável polymer locust bean gum (LBG) e hidroxipropilmetil celulose (HPMC) como materiais de revestimento. Os comprimidos de desintegração rápida contendo 50 mg de fluoruracila foram revestidos por compressão com LBG e HPMC em diferentes proporções (8:1, 7:2 e 6:3), com peso de cobertura de 300, 400 e 500 mg. Os dados da dissolução in vitro indicaram que a formulação (CLH63) com peso de cobertura de 500 mg contendo LBG e HPMC na proporção de 6:3 forneceu o melhor perfil de liberação (0% nas primeiras 5 horas e 96,18% em 24 horas). Os resultados de DSC e de FTIR não indicaram interação entre o fármaco e os polímeros ou outros excipientes. Os estudos de raios X in vivo revelaram que a formulação CLH63 foi capaz de resistir à quebra no estômago e no intestino delgado. A desintegração do comprimido ocorreu no cólon, entre 8 e 16 horas após a administração da dose. Pelo presente estudo, concluiu-se que os comprimidos de fluoruracila revestidos com LBG e HPMC por compressão se constituirão em estratégia útil na liberação de fluoruracila no cólon, para o tratamento seguro e efetivo do câncer de cólon, sem que o fármaco seja liberado na região gastrointestinal superior.

Development of enteric coated sustained release minitablets containing mesalamine

The aim of this study was to develop and evaluate a multiparticulate modified release system, composed of minitablets with a sustained release matrix system coated with a pH-dependent release polymer, using mesalamine as a model drug. Polyox® WSR 1105 was the polymer used in the matrix system and Eudragit® L30D55 was used as a pH-dependent polymer. The minitablets (with 20%, 30% or 40% Polyox® concentration) were prepared by dry granulation, which led to good quality minitablets. The developed minitablets were coated in a fluidized bed at 8% of the coating level. Dissolution studies were performed in media that simulated the gastrointestinal tract (pH 1.4, 6.0 and 7.2) and showed that formulations with higher Polyox® concentrations were capable of retaining the drug release in pH 1.4. All formulations prolonged the drug release and presented zero-order kinetic behaviour. The Korsmeyer-Peppas model demonstrated that formulations with 20% or 30% of polymer exhibited anomalous transport behaviour, whilst the 40% sample exhibited super case II model transportation. Dissolution efficiency showed that only the formulations containing 20% and 40% polymer could be considered statistically different.

O presente trabalho teve como objetivo desenvolver e avaliar um sistema multiparticulado de liberação modificada, composto por minicomprimidos com sistema matricial de liberação prolongada revestidos com polímero de liberação pH-dependente, utilizando mesalazina como fármaco modelo. Polyox® WSR 1105 foi o polímero utilizado no sistema matricial e Eudragit® L30D55 foi utilizado como polímero pH-dependente. Os minicomprimidos (com 20%, 30% e 40% de concentração de Polyox®) foram preparados por granulação via seca, gerando minicomprimidos de boa qualidade. Os minicomprimidos desenvolvidos foram revestidos em leito fluidizado a 8% de nível de revestimento. Efetuou-se o estudo de dissolução em meios que simulam o trato gastrointestinal (pH 1,4, 6,0 e 7,2) e as formulação contendo maiores concentrações de Polyox® foram capazes de reter a liberação do fármaco em pH 1,4. Todas as três formulações apresentaram liberação prolongada e comportamento cinético de ordem zero. O modelo de liberação de Korsmeyer-Peppas mostrou que as formulações com 20% e 30% de polímero apresentam comportamento de transporte anômalo, enquanto a com 40%, transporte super caso II. A eficiência de dissolução mostrou que somente as formulações com 20% e 40% de concentração do polímero foram consideradas estatisticamente diferentes.

The evaluation of coated granules to mask the bitter taste of dihydroartemisinin / A avaliação de grânulos revestidos para mascarar o sabor amargo da diidroartemisina

The purpose of this study was to mask the bitter taste imparted by dihydroartemisinin (DHA) by the use of different coating materials. Trial-1 and trial-2 were conducted to prepare the DHA granules. The granules produced from trial-1 were irregular in shape and smaller in size while the trial-2 granules were more regular and larger in size. The granules obtained from both trials were then coated with two different coating methods, namely A and B, depending upon coating material. The trial-2 granules showed better flow properties than trial-1 granules. In vitro dissolution studies in phosphate buffer at pH 6.8 revealed that granules of trial-2B released only 34 percent ± 3 DHA in two minutes compared with trial-1A (57 percent ± 2), trial-1B (48 percent ± 2) and trial-2A (53 percent ± 7). The pleasant taste perception (PTP) test also confirmed the taste masking efficacy of trial-2B (P < 0.05). Scanning electron microscopy (SEM) revealed the more regular and smooth surface of trial-2B granules. In addition, the differential thermal and thermogravimetric analysis (TG-DTA) confirmed no interaction between the materials and pure DHA. DHA has shown its characteristic peaks in the x-ray diffraction (XRD) patterns which were also prominent in all the granules. In conclusion, the granules obtained from trial-2B displayed considerable decrease in the bitter taste of DHA thereby fulfilling the purpose of this study.

O objetivo deste estudo foi o de mascarar o gosto amargo característico da diidroartemisinina (DHA) pelo uso de diferentes materiais de revestimento. Experimento-1 e experimento-2 foram realizados para preparar grânulos de DHA. Os grânulos produzidos pelo experimento-1 mostraram-se irregulares e menores se comparados aos obtidos pelo experimento-2, que foram mais regulares e maiores. Os grânulos obtidos em ambos os experimentos foram, então, revestidos por dois métodos distintos de revestimento, designados como A e B, dependendo do material de revestimento empregado. Os grânulos do experimento-2 mostraram melhor propriedade de fluxo que os obtidos no experimento-1. Estudos de dissolução in vitro em tampão fosfato pH 6,8 revelaram que grânulos do experimento-2B liberaram apenas 34 por cento ± 3 da DHA em dois minutos se comparado com experimento-1A (57 por cento ± 2), experimento-1B (48 por cento ± 2) e experimento-2A (53 por cento ± 7). A Análise Sensorial quanto ao sabor (Pleasant Taste Perception - PTP) também confirmou a eficácia do experimento-2B (P <0,05) em mascarar o gosto amargo da DHA. Microscopia Eletrônica de Varredura (SEM) revelou a superfície mais regular e lisa dos grânulos obtidos pelo experimento-2B. Além disso, Análise Termogravimétrica e Análise Térmica Diferencial (TG-DTA) confirmaram que não há nenhuma interação entre os materiais e a DHA pura. DHA mostrou seus picos característicos na Difração de Raios X (XRD) em padrões que também foram proeminentes em todas as amostras. Em conclusão, os grânulos obtidos pelo experimento-2B exibiram diminuição considerável no gosto amargo da DHA, o que era o propósito deste estudo.

Development and validation of dissolution method for carvedilol compression-coated tablets

The present study describes the development and validation of a dissolution method for carvedilol compression-coated tablets. Dissolution test was performed using a TDT-06T dissolution apparatus. Based on the physiological conditions of the body, 0.1N hydrochloric acid was used as dissolution medium and release was monitored for 2 hours to verify the immediate release pattern of the drug in acidic pH, followed by pH 6.8 in citric-phosphate buffer for 22 hours, to simulate a sustained release pattern in the intestine. Influences of rotation speed and surfactant concentration in medium were evaluated. Samples were analysed by validated UV visible spectrophotometric method at 286 nm. 1 percent sodium lauryl sulphate (SLS) was found to be optimum for improving carvedilol solubility in pH 6.8 citric-phosphate buffer. Analysis of variance showed no significant difference between the results obtained at 50 and 100 rpm. The discriminating dissolution method was successfully developed for carvedilol compression-coated tablets. The conditions that allowed dissolution determination were USP type I apparatus at 100 rpm, containing 1000 ml of 0.1N HCl for 2 hours, followed by pH 6.8 citric-phosphate buffer with 1 percent SLS for 22 hours at 37.0 ± 0.5 ºC. Samples were analysed by UV spectrophotometric method and validated as per ICH guidelines.

O presente estudo descreve o desenvolvimento e a validação de método de dissolução para comprimidos revestidos de carvedilol. O teste de dissolução foi efetuado utilizando-se o aparelho para dissolução TDT-06T. Com base nas condições fisiológicas do organismo, utilizou-se ácido clorídrico 0,1 N como meio de dissolução e a liberação foi monitorada por 2 horas para se verificar o padrão de liberação imediata do fármaco em condições de pH baixo, seguidas por pH 6,8 em tampão cítrico-fosfato por 22 horas, para simular o padrão de liberação controlada no intestino. Avaliou-se a influência da velocidade de rotação e a concentração de tensoativo no meio. As amostras foram analisadas por método espectrofotométrico UV-visível validado, em 286 nm. O laurilsulfato sódico a 1 por cento (SLS) mostrou-se ótimo para aumentar a solubilidade do carvedilol em pH 6,8 em tampão cítrico-fosfato. A análise da variância não mostrou diferença significativa entre os resultados obtidos a 50 e a 100 rpm. O método da dissolução discriminante foi desenvolvido com sucesso para os comprimidos revestidos de carvedilol. As condições que permitiram a determinação da dissolução foram: aparelho USP tipo I a 100 rpm, contendo 1000 mL de HCL 0,1 N por 2 horas, seguido de pH 6,8 com tampão cítrico-fosfato, com 1 por cento de SLS por 22 horas a 37,0 ± 0,5 ºC. Amostras foram analisadas por método espectrofotométrico e validadas pelas normas ICH.

LC determination of entacapone in tablets: in vitro dissolution studies.

The aim of the study was to develop and validate a dissolution procedure for entacapone-coated tablets. Several conditions such as medium composition, pH, surfactant concentration, and rotation speed were evaluated. The best dissolution conditions were achieved using apparatus 2, 900 mL of medium containing acetate buffer pH 5.3 at a rotation speed of 50 rpm, and a reversed-phase liquid chromatographic method for the quantification of the drug from the dissolution test, as well as to evaluate the dissolution profiles for tablets. The procedure was validated by specificity, linearity, accuracy, repeatability, intermediate precision, and robustness. The chromatographic method employed an Agilent Eclipse XDB RP-18 (150 × 4.6 mm i.d., particle size 5 µm) with a mobile phase consisting of water pH 3.0 and acetonitrile (65:35, v/v) at a flow rate of 2.0 mL/min. The dissolution procedure developed and validated was adequate for its purpose and could be applied for quality control for entacapone-coated tablets because there is no official monograph.

In-vivo gamma scintigraphic evaluation and determination of a gastro-resistant etodolac tablet in humans.

A gastro-resistant (enteric coated) etodolac tablet dosage form, was evaluated by using in vitro and in vivo methods. In vitro drug release studies have shown that enteric coated tablet dosage form protects the drug from being released under conditions mimicking stomach to small intestine transit. The gastro-intestinal transit of radiolabeled 300 mg enteric coated etodolac tablets in six healthy, fed and fasted state volunteers was monitored using external gamma camera. Dosage form position was reported at several time intervals. Etodolac serum concentrations were determined from serum samples drawn over 420 min following dosing. Differences in gastro-intestinal transit between fed and fasted volunteers had little effect on etodolac bioavailability. AUC, Tmax and C max values were calculated for both types of studies.

Magnetic marker monitoring: high resolution real-time tracking of oral solid dosage forms in the gastrointestinal tract.

Knowledge about the performance of dosage forms in the gastrointestinal tract is essential for the development of new oral delivery systems, as well as for the choice of the optimal formulation technology. Magnetic Marker Monitoring (MMM) is an imaging technology for the investigation of the behaviour of solid oral dosage forms within the gastrointestinal tract, which is based on the labelling of solid dosage forms as a magnetic dipole and determination of the location, orientation and strength of the dipole after oral administration using measurement equipment and localization methods that are established in biomagnetism. MMM enables the investigation of the performance of solid dosage forms in the gastrointestinal tract with a temporal resolution in the range of a few milliseconds and a spatial resolution in 3D in the range of some millimetres. Thereby, MMM provides real-time tracking of dosage forms in the gastrointestinal tract. MMM is also suitable for the determination of dosage form disintegration and for quantitative measurement of in vivo drug release in case of appropriate extended release dosage forms like hydrogel-forming matrix tablets. The combination of MMM with pharmacokinetic measurements (pharmacomagnetography) enables the determination of in vitro-in vivo correlations (IVIC) and the delineation of absorption sites in the gastrointestinal tract.