Formulation, Optimization, in vitro and in-vivo evaluation of levofloxacin hemihydrate Floating Tablets

Abstract The objective of the present investigation was to design, optimize and characterize the gastro retentive floating levofloxacin tablets and perform in-vivo evaluation using radiographic imaging. The floating tablets were prepared by using polymers i.e hydroxy propyl methyl cellulose (HPMC-K4M) and carbopol-940 individually and in combination by nonaquous granulation method. All the Formulations were evaluated for swelling index (S.I), floating behavior and in-vitro drug release kinetics. The compatibility study of levofloxacin with other polymers was investigated by FTIR, DSC, TGA and XRD. Results from FTIR and DSC revealed no chemical interaction amongst the formulation components. The optimized formulation (F11) showed floating lag time (FLT), total floating time (TFT) swelling index (S.I) of 60 sec, >16h and approximately 75 %, respectively. Moreover, F11 showed zero order levofloxacin release in simulated gastric fluid over the period of 6 h. X-ray studies showed that total buoyancy time was able to delay the gastric emptying of levofloxacin floating tablets in rabbits for more than 4 hours. In conclusion the optimized formulation (F11) can be used for the sustained delivery of levofloxacin for the treatment of peptic ulcer.

Intra and Extra-granular Disintegrant Properties of Modified Underutilised Red Lima Bean Starch in Paracetamol Tablet Formulation

Abstract Red lima bean (Phaseolus lunatus Linn) Family Fabaceae, has been modified by succinylation and annealing, and used as intra- and extra-granular disintegrants at concentrations of 5 and 10 %w/w in paracetamol tablet formulation in comparison with corn starch BP. The starches were characterised using FT-IR spectroscopy, SEM, proximate analysis, physicochemical and functional properties. FT-IR spectrometry revealed characteristic peaks at 1575.53 and 1713.99 cm-1 for the succinylated starch while the annealed showed no significant difference from the native starch. Modifications did not alter the ovoid shape of the native starch but reduced the particle size. Succinylation improved water absorption capacity, solubility and swelling of lima bean starch but annealing reduced the parameters. Tablets with disintegrants of lima bean starches generally had higher crushing strengths and lower friability than tablets with corn starch. Modifications reduced the disintegration time of the tablets when the starches were incorporated intra-granularly, which suggested particle-particle bond interruption and destruction of hydrogen bonds as mechanism of disintegration. Tablets containing 10 %w/w succinylated red lima bean starch incorporated intra-granularly had the highest disintegration efficiency ratio, DER, indicating a great balance between mechanical and disintegration properties. Modified red lima bean starches incorporated intra-granularly into paracetamol tablets led to faster disintegration and could efficiently substitute corn starch as disintegrant.

Evaluation of physicochemical and microbiological stability of liquid preparation from tizanidine hydrochloride tablets - a Hospital concern

Tizanidine hydrochloride is a centrally acting skeletal muscle relaxant, used in the management of spasticity. This drug is commercially available only as tablets, which highlights the need to develop oral liquid formulations. In the hospital environment, this aspect is circumvented by the preparation of suspensions, to allow administration to children and adults with impaired swallowing, but there are no data regarding their stability. The purpose of this study was to evaluate the physicochemical andmicrobiological stability of liquid dosage forms prepared in the hospital environment from tizanidine hydrochloride tablets, applying high performance liquid chromatography (HPLC) and microbiological analysis. A simple and stability-indicating HPLC method was developed and validated for specificity, linearity, limits of detection and quantification, precision, accuracy and robustness. The liquid formulations were placed in amber PET and glass bottles, which were stored under three different conditions: at room temperature, under refrigeration and at 40 ºC. The liquid formulations were analyzed and demonstrated chemical stability for 56 days, allowing their use for long periods. However, the determination of microbiological stability showed that these formulations are prone to microbial contamination, which has dramatically reduced its stability to 7 days, in both bottles and at all evaluated temperatures

Formulation and evaluation of a mucoadhesive buccal tablet of mefenamic acid

Buccal route of administration has many advantages such as improving patient compliance, bypassing the GIT and hepatic first pass effect. The objectives are to formulate mucoadhesive buccal tablet using Mefenamic acid and compatible excipients, and to evaluate the product using quality control tests and in vitro tests. The ingredients were subjected to Differential Scanning Calorimetry and Fourier Transform Infrared Spectroscopy studies for compatibility test and the results showed no interaction. Two batches of mefenamic buccal tablet were prepared. The tablet thickness and diameter are 3.75 mm and 12 mm respectively. All tablets are within the specification of +/- 5%. The in-house tablet hardness is 6.8-15kg and percent friabilation is not more than 0.8%. The disintegration test showed that all tablets disintegrated within 4 hours. The content uniformity showed that tablets are within the range of 85%-115%. The tablet weight is within the 5% range. The percent swelling is 53.83% to 58.86% and moisture absorption is 14.79% to 15.56%. The surface pH of the tablet is close to the salivary pH, which means that it would not irritate the buccal mucosa. The buccal tablet has a mucoadhesiveness of 0.196 to 0.200. There was no change in pH and size after subjecting it to stability studies in human saliva. Drug release studies showed 80.7% to 83.4% after 3 hours. Even after 3 months of subjecting the tablets to 40 ºC and 75% RH, results are within acceptable range. The results show the potential of the formulation as a mucoadhesive buccal tablet.

Development of fast dissolving tablets of flurbiprofen by sublimation method and its in vitro evaluation

Flurbiprofen belongs to Biopharmaceutical Classification System (BCS) class II drugs which are poorly soluble in water. The objective of present research work was to prepare fast dissolving tablets of Flurbiprofen using varying concentrations of three different sublimating agents to improve the dissolution rate. Seven formulations were prepared containing different concentrations of camphor, ammonium bicarbonate and thymol as sublimating agent along with primogel as a superdisintegrant. Tablets were manufactured by direct compression method. The prepared tablets were evaluated for pre-compression and post-compression parameters result, For all formulations result was within official limits. FTIR studies revealed that there were no interactions between the drug and the excipients used. From in vitro drug release studies it was concluded that the formulations F6 and F7 containing 10% and 15% of thymol showed fast drug release of 100.00% and 100.84% respectively in 30 minutes. Formulations containing camphor (F2 & F3) and ammonium bicarbonate (F4 & F5) as sublimating agents showed a drug release of less than 80%, while the control formulation F1 having no sublimating agent showed 49.14% of drug release in 30 minutes. Thus thymol can successfully be used to formulate fast dissolving tablets of flurbiprofen by sublimation method with much better dissolution profile

Pharmaceutical development of tablets containing a spray-dried optimized extract from Lippia origanoides H. B. K.: influence of excipients and toxicological assessment

ABSTRACT Lippia origanoides is a honey shrub which has showed hypotensive potential assessed by in vivo studies. The aim of this work is the development of a pharmaceutical formulation composed by an optimized extract obtained from aerial parts of L. origanoides. The quantification of the naringenin marker in the dry extract and tablets developed was performed, as well as the assessment of the oral acute toxicity in rats. The hydroalcoholic extract of L. origanoides was spray-dried with the addition of colloidal silicon dioxide (Lo-HAE/CSD), and then applied in the preparation of eight different lots of tablets. The influence of the diluent (cellulose or babassu mesocarp), the presence of binder, and the percentage of lubricant, as well as organoleptic and physicochemical characteristics were screened. For the quantification of the marker content both in Lo-HAE/CSD and in the tablets, an analytical curve of the naringenin standard was fitted, and the samples were then analyzed in UFLC. The toxicological assessment was performed in female Wistar rats according to the Acute Toxic Class Method from OECD. The developed tablets produced meet acceptable macroscopic characteristics, and the presence of babassu as diluent provided improved physicochemical properties. The best content of Lo-HAE/CSD in the tablet (100.27%) was identified for the lot containing babassu, composed by 1.0% magnesium stearate, without PVP binder in its formulation. Moreover, Lo-HAE/CSD showed no signs of toxicity. Therefore, the babassu mesocarp powder is a promising pharmaceutical excipient for the development of herbal tablets containing the Lippia origanoides extract.

Desenvolvimento e caracterização de filmes e comprimidos bucais a base de pectina e goma gelana para liberação tópica de triancinolona / Development and characterization of films and buccal tablets based on pectin and gellan gum for the topical release of triamcinolone

O tratamento farmacológico de patologias bucais é conduzido, geralmente, por via de adminis-tração local. No entanto, devido ao pouco tempo de permanência do fármaco no local de ação, esse tratamento pode ser bastante comprometido. Assim, este trabalho teve por objetivo o de-senvolvimento de formas farmacêuticas que proporcionem a liberação local de triancinolona na cavidade oral. Foram produzidos filmes e comprimidos mucoadesivos a partir de polímeros naturais como gelana e pectina. Os filmes bucais foram preparados por meio de evaporação do solvente (solvent casting) utilizando diferentes quantidades de polímeros. As matérias-primas e os filmes foram caracterizados fisico quimicamente utilizando espectroscopia vibracional (in-fravermelho com transformada de Fourier e Raman) e difração de raios X. As propiedades físicas e mecânicas dos filmes também foram avaliadas. Além disso, realizou-se os ensaios de mucoadesividade e de dissolução do fármaco. Os comprimidos foram preparados por com-pressão direta usando como base os polímeros naturais. Diferentes parâmetros em relação as misturas e as formulações foram avaliados tais como as propriedades de fluxo dos pós consti-tuintes, peso médio, dureza, friabilidade e desintegração. Em relação aos filmes bucais, estes foram obtidos com sucesso através de um método simples, sem a utilização de agentes reticu-lantes, ácidos ou solventes orgânicos. Todos apresentaram bons resultados nas propriedades avaliadas, no entanto as formulações com quantidades intermediarias de polímeros foram as melhores. Dentre as formulações de comprimidos preparadas, apenas 4 apresentaram boas ca-racterísticas, no entanto, os resultados dos ensaios de dissolução mostraram que estas formula-ções têm capacidade de agir como sistema de liberação controlada de fármacos.

Pharmacological treatment of oral pathologies is usually conducted by local administration. However, due to the short time the drug stays in the site of action, this treatment can be quite compromised. Thus, the objective of this work was to develop pharmaceutical forms that pro-vide the local release of triamcinolone in the oral cavity. Mucoadhesive films and tablets were made from natural polymers such as gellan and pectin. The buccal films were prepared by sol-vent casting using different amounts of polymers. The raw materials and films were characte-rized physically chemically using vibrational spectroscopy (FTIR and Raman) and X-ray diffraction. The physical and mechanical properties of the films were also evaluated. In addi-tion, the mucoadhesive and drug dissolution tests were performed. The tablets were prepared by direct pressing with the natural polymers. Different parameters in relation to mixtures and formulations were evaluated such as the flow properties of the constituent powders, average weight, hardness, friability and disintegration. In relation to oral films, these were successfully obtained by a simple method, without the use of crosslinking agents, acids or organic solvents. All presented good results in the evaluated properties, however the formulations with interme-diate amounts of polymers were the best. Among the tablet formulations prepared, only 4 sho-wed good characteristics, however, the dissolution test results showed that these formulations have the ability to act as a controlled drug delivery system.

Development and validation of alternative methods by non-aqueous acid-base titration and derivative ultraviolet spectrophotometry for quantification of sildenafil in raw material and tablets

Sildenafil citrate (SILC) is a potent phosphodiesterase-5 inhibitor used for erectile dysfunction and pulmonary hypertension. This study shows two simple, fast and alternative analytical methods for SILC determination by non-aqueous titration and by derivative ultraviolet spectrophotometry (DUS) in active pharmaceutical ingredient and/or dosage forms. The quantitation method of SILC active pharmaceutical ingredient by non-aqueous acid-base titration was developed using methanol as solvent and 0.1 mol/L of perchloric acid in acetic acid as titrant. The endpoint was potentiometrically detected. The non-aqueous titration method shows satisfactory repeatability and intermediate precision (RSD 0.70-1.09%). The neutralization reaction occurred in the stoichiometric ratio 1:1 in methanol. The determination of SILC active pharmaceutical ingredient or dosage forms by DUS was developed in the linear range from 10 to 40 µg/mL, in 0.01 mol/L HCl, using the first order zero-peak method at λ 256 nm. The DUS method shows selectivity toward tablets excipients, appropriate linearity (R2 0.9996), trueness (recovery range 98.86-99.30%), repeatability and intermediate precision in three concentration levels (RSD 1.17-1.28%; 1.29-1.71%, respectively). Therefore, the methods developed are excellent alternatives to sophisticated instrumental methods and can be easily applied in any pharmaceutical laboratory routine due to simple and fast executions.

Development and validation of a stability indicating HPLC method to determine diltiazem hydrochloride in tablets and compounded capsules

ABSTRACT A stability indicating HPLC method to determine diltiazem hydrochloride (DTZ) in tablets and compounded capsules was developed and validated according to Brazilian and the International Conference on Harmonization (ICH) guidelines. The separation was carried out on a Purospher Star® C18 (150 x 4.6 mm i.d., 5 µm particle size, Merck Millipore) analytical column. The mobile phase consisted of a 0.05% (v/v) trifluoroacetic acid aqueous solution and a 0.05% trifluoroacetic acid methanolic solution (44:56, v/v). The flow rate was 1.0 mL.min-1 with a run time of 14 minutes. The detection of DTZ and degradation products (DP) was performed at 240 nm, using a diode array detector. The method proved to be linear, precise, accurate, selective, and robust, and was adequate for stability studies and routine quality control analyses of DTZ in tablets and compounded capsules.

Analysis of spironolactone polymorphs in active pharmaceutical ingredients and their effect on tablet dissolution profiles

ABSTRACT Spironolactone (SPR) is a steroidal drug administered as a potassium-sparing diuretic for high blood pressure treatment. The drug shows incomplete gastrointestinal absorption due to its poor aqueous solubility. The physicochemical properties of SPR in crystal forms I and II suggest that differences in their aqueous solubility may lead to a lack of bioequivalence between solid-state formulations. In this study, SPR polymorphs in five batches of active pharmaceutical ingredients (APIs) from three manufacturers were characterized using powder X-ray diffraction, infrared spectroscopy, thermal analysis, and solubility measurements. SPR tablets (50 mg) were manufactured in our laboratory using API in pure form II, and API in form II contaminated with form I, which was found in a commercial batch. Physicochemical quality evaluations of the manufactured tablets, along with five SPR tablets marketed in Brazil, were performed, and results indicated differences in their dissolution profiles. In the manufactured tablets, differences were associated with the increased solubility of API in form II contaminated with form I compared to API in pure form II. In the marketed SPR tablets, the formulation composition demonstrated an important role in the dissolution rate of the drug, leading to lack of pharmaceutical equivalence among the drug products.

Comparación de los perfiles de disolución de comprimidos de lamotrigina de 100mg comercializados en Paraguay / Comparison of the dissolution profiles of tablets of lamotrigine 100mg traded in Paraguay

Objetivo: evaluar los perfiles de disolución decomprimidos de Lamotrigina 100mg (Test) con laReferencia (Lamictal®) comercializados en Paraguay.Material y Métodos: Se utilizaron comprimidosde Lamotrigina de 100mg comercializados enParaguay. Se determinaron los perfiles de disoluciónde los productos Test y Referencia, en los tresmedios de disolución recomendados (pHs 1,2 ; 4,5y 6,8). El método analítico se basó en HPLC condetector PDA a 277nm, usando una PhenomenexLuna C18 a 40ºC, con fase móvil de buffer fosfatode sodio 0.05M pH4.0-acetonitrilo (80:20), flujode 1.3mL/min y tiempo de retención de 5 min.Resultados: Los perfiles de disolución del productoTest de Lamotrigina 100mg, fueron similaresen los diferentes pHs al producto de Referencia,liberando más del 85% a los 15 minutos en los 3medios de disolución, no siendo necesaria la comparacióncon el factor f2.Conclusión: Los perfiles de disolución de los comprimidosde Lamotrigina de 100mg Test muestranun comportamiento in vitro semejante al productode Referencia, lo que sugiere que su comportamientoin vivo podría ser también semejante.

Objectives: to evaluate the dissolution profiles ofLamotrigine tablets of 100 mg (Test) and Reference(Lamictal®) marketed in Paraguay.Material and Methods: Tablets of Lamotrigine100 mg marketed in Paraguay were used. Dissolutionprofiles of the Test and Reference productswere determined in the three recommended dissolutionmedia (pH 1.2; 4.5 and 6.8). The HPLCmethod used consisted of a Phenomenex Luna C18column, with mobile phase of 0.05M sodium phosphatebuffer pH4.0-acetonitrile (80:20), flow rateof 1.3mL / min and retention time of 5 min. Thecolumn compartment was kept at 40ºC, and thewavelength detection was 277 nm.Results: The dissolution profiles of the Test productof Lamotrigine 100mg, showed similar behavior tothe Reference product at the three different pHs,releasing more than 85% in 15 minutes in the threemedia dissolution. No calculation using the similarityfactor f2 was needed.Conclusion: Dissolution profiles of the two formulationsof Lamotrigine 100mg were similar in thedifferent pH dissolution media, thus a similar invivo behavior could be expected.

Diseño y preparación de formas farmacéuticas sólidas de Benznidazol para el tratamiento de la Enfermedad de Chagas / Design and Preparation fo Pharmaceutical Solid Dosage Forms of Benznidazole for the Treatment of Chagas Disease

INTRODUCCIÓN: En Argentina se emplea el benznidazolcomo terapéutica de primera línea para el tratamiento etiológico del Chagas. Desde su lanzamiento (hace más de 40 años), sólo se dispone de comprimidos convencionales de 100 mg; no se han desarrollado nuevas formas farmacéuticas que aumenten la eficacia y seguridad, ni alternativas con dosis pediátricas. OBJETIVOS: Desarrollar formas farmacéuticas de benznidazol que ofrezcan ventajas farmacoterapéuticas. MÉTODOS: Preformulación y diseño de nuevas formulaciones de benznidazol, con caracterización físico-química y selección de las formulaciones más favorables. Frente a la discontinuidad de producción del ingrediente activo benznidazol, se desarrolló una metodología de extracción a partir de 8520/8520/nica alternativa comercial disponible. RESULTADOS: Se obtuvieron nuevas formulaciones de comprimidos de 50 y 100 mg debenznidazol, con una rápida disolución del producto de referencia. Además, se obtuvieron formulaciones masticables de 50 mg bajo la forma de hidrogeles azucarados, con un efectivo enmascaramiento del mal sabor. Todas las formulaciones cumplieron los ensayos de evaluación de las propiedades farmacotécnicas y biofarmacéuticas, superando los perfiles de referencia. CONCLUSIONES: Se desarrollaron nuevas alternativas farmacéuticas de benznidazol de rápida disolución, que podrían mejorar el tratamiento etiológico de la enfermedad(especialmente en pediatría) y convertirse en herramientas aptas para su explotación comercial

INTRODUCTION: In Argentina, benznidazole is the drug of choice for the etiological treatment of Chagas disease. Since it was launched (more than 40 years ago), there are only 100 mg tablets available; the development included neither new pharmaceutical forms improving efficacy and safety, nor a pediatric dosage option. OBJECTIVES: To develop pharmaceutical form sof benznidazole with pharmacotherapeutic advantages. METHODS: Preformulation and design of new formulation sof benznidazole, with physicochemical characterization and selection of the most favorable formulations. Due to the discontinuity in the production of the active ingredient benznidazole, a specific methodology was developed in order to obtain it from the only commercially available alternative. RESULTS: New benznidazole tablet formulations were obtained (50 and 100 mg), with a rapid dissolution of the reference product, as well as chewable formulation sof 50 mg as sugar hydrogels featuring an effective taste masking. All formulations passed the evaluation tests for pharmacotechnical and biopharmaceutical properties, out performing the reference profiles. CONCLUSIONS:New fast-dissolving pharmaceutical dosage forms of benznidazole were developed, which could improve the etiological treatment of the disease (especially in the pediatric field) and become a proper tool for its commercial exploitation

Comprimidos contendo microesferas de cetoprofeno como sistema de liberação bifásica / Tablets containing ketoprofen microspheres as abiphasic delivery system

Sistema de liberação bifásica é aquele que promove a liberação do fármaco em dois estágios: um de liberação imediata e o outro de liberação prolongada. No presente trabalho o cetoprofeno foi incorporado em microesferas de Kollidon® SR e acetobutirato de celulose e, posteriormente, as microesferas foram comprimidas com o intuito de obter comprimidos de liberação bifásica. As microesferas foram obtidas através do método de emulsão e evaporação do solvente óleo em água (O/A), originando partículas esféricas e eficiência de encapsulação de 81,9%, indicando que o processo de obtenção permitiu uma incorporação bastante eficiente do fármaco nas microesferas. Três formulações (F) de comprimidos foram obtidas por compressão direta utilizando-se uma prensa hidráulica: F1 - contendo as microesferas de cetoprofeno; F2 - contendo microesferas de cetoprofeno, crospovidona e celulose microcristalina; e F3 - contendo as microesferas de cetoprofeno, o cetoprofeno não encapsulado, além dos excipientes citados anteriormente (comprimidos bifásicos). Análises por microscopia eletrônica de varredura evidenciaram que o processo de compressão não afetou a morfologia das microesferas, as quais mantiveram sua integridade. A liberação do fármaco a partir dos comprimidos bifásicos inicialmente foi rápida, com 75% do fármaco dissolvido em uma hora, seguida de uma liberação prolongada, atingindo 88% de fármaco dissolvido em doze horas. Os resultados obtidos sugerem que o sistema proposto pode ser otimizado para a liberação do cetoprofeno em dois estágios, para administração por via oral.

A biphasic delivery system is one from which a drug is released in two stages, consisting of an immediate release and a prolonged release. In this study, ketoprofen was incorporated into Kollidon SR® and cellulose acetate butyrate microspheres, which were then compressed in order to obtain biphasic release tablets. The microspheres were produced by an oil-in-water (O/W) emulsion and solvent evaporation method, resulting in spherical particles and an encapsulation efficiency of 81.9%, indicating that the process allowed a very efficient incorporation of the drug into the microspheres. Three tablet formulations were compounded by direct compression in a hydraulic press: F1, containing only the ketoprofen microspheres; F2, containing ketoprofen microspheres, crospovidone and microcrystalline cellulose, and F3, containing the ketoprofen microspheres plus non-encapsulated ketoprofen, together with the aforementioned excipients (biphasic tablets). Examination by scanning electron microscopy showed that the compression process did not affect the morphology of the microspheres, which remained whole and undamaged. The drug release from the biphasic tablets was initially rapid, 75% of the drug being dissolved in one hour, followed by a sustained slow release, 88% of the drug being dissolved in twelve hours. These results suggest that the proposed delivery system can be optimized for two-stage ketoprofen release via oral administration.

Antimicrobial activity assessment of time-dependent release bilayer tablets of amoxicillin trihydrate

The aim of present study was the assessment of antimicrobial activity of prepared time-dependent release bilayer tablets of amoxicillin trihydrate and in vitro evaluation of drug release by antimicrobial assay using agar plate diffusion method. The bilayer tablets comprised of a delayed and sustained release layer. Direct compression method was used for the preparation of bilayer tablets containing Eudragit-L100 D55 as delayed release polymer, and HPMCK4M and HPMCK15 as sustained release polymers. The prepared bilayer tablets containing amoxicillin trihydrate were evaluated for hardness, thickness, friability, weight variation and drug content. Further, in vitro drug release was assessed by antimicrobial assay using S. aureus and E. coli as test microorganisms. The aliquot samples of in vitro drug release study were found to be effective against both microorganisms for 16 hours due to sustained action. The in vitro drug release study and antimicrobial assay showed that bilayer tablets have sustained release profile of drug delivery with time-dependent burst release after a lag-time of 2 hours. The lower MIC value (2 µg/mL) of prepared bilayer tablets vis-à-vis marketed preparation (5 µg/mL) represented its good antimicrobial activity.

O objetivo do presente estudo foi avaliar a atividade antimicrobiana de formulações de comprimidos de dupla camada contendo amoxicilina triidratada para liberação tempo dependente e avaliação da liberação in vitro do fármaco pelo ensaio de atividade antimicrobiana utilizando o método de difusão em placa de ágar. Os comprimidos de dupla camada consistem em uma camada para liberação retardada e outra sustentada. O método de compressão direta foi usado para a preparação dos comprimidos de dupla camada contendo Eudragit-L 100 D55 como polímero para liberação retardada e HPMCK4M ou HPMCK15 como polímeros para liberação sustentada. As formulações de comprimidos de dupla camada contendo amoxicilina triidratada foram avaliadas quanto a dureza, espessura, friabilidade, variação de peso e conteúdo de fármaco. Além disso, a liberação do fármaco in vitro foi avaliada por ensaio de atividade antimicrobiana usando S. aureus e E. coli como microrganismos teste. A alíquota das amostras do estudo de liberação do fármaco in vitro demonstrou ser efetiva contra ambos os microrganismos por um período de 16 horas devido à ação sustentada. O estudo de liberação do fármaco in vitro e o ensaio de atividade antimicrobiana mostraram que os comprimidos de dupla camada tiveram um perfil de liberação sustentada do fármaco com um pico de liberação após 2 horas de ensaio. O menor valor de MIC (2 ug/mL) dos comprimidos de dupla camada quando comparados à formulação comercial (5 ug/mL) representa uma boa atividade antimicrobiana.

Sistema de liberação prolongada a partir de comprimidos matriciais bioadesivos vaginais contendo metronidazol / Sustained release system from vaginal bioadhesive matrix tablets containing metronidazole

A vaginose bacteriana é a mais comum das infecções do trato genital feminino.O metronidazol, droga de escolha no tratamento, possui boa resposta terapêutica, mas, devido à sua toxicidade após doses contínuas, tem sua capacidade de combate e reversão da doença limitada pela efemeridade do tratamento.Desenvolveu-se a forma farmacêutica comprimido matricial bioadesivo vaginal contendo metronidazol que levou em conta, tanto a redução das quantidades administradas da droga, quanto o uso de atributos que desfavoreçam a permanência da flora patógena no meio vaginal, como a liberação prolongada e a acentuada adesão da forma à mucosa.Foram obtidos durante o estudo três formulações chamadas de lotes de bancada (LB I, LB II e LB III) com variações quali-quantitativas dos excipientes utilizados.Nos LB I e LB II utilizou-se o hidropropilmetilcelulose e carbopol como constituintes da matriz, porém no LB III foi utilizado uma composição de hidropropilmetilcelulose, etilcelulose e carbopol.As formulações apresentaram resultados dentro das especificações frente aos testes físico-químicos habituais de acordo com a Farmacopéia brasileira.Os comprimidos LB I e LB II liberaram todo seu conteúdo após seis e 12 horas, respectivamente, a partir de matrizes de caráter notadamente adesivo e ao fim dos ensaios mantiveram-se na forma de pequena estrutura gelificada.Mesmo sob essas condições, e após 48 horas de ensaio, a formulação LB III não liberou todo seu conteúdo, pode-se levar em conta a mudança da natureza dos componentes da matriz assim como a necessidade de um desenvolvimento e validação de método mais específico para dissolução

Uso da caseína e acilderivados da caseína como excipiente para sistemas matriciais / Use of casein and its acylderivatives as excipients for matrix systems

O desenvolvimento tecnológico de novas formas farmacêuticas capazes de modular a liberaçÝo de fármacos tem atraído um grande interesse dos cientistas farmacêuticos. Uma das maneiras de modificar a liberaçÝo do fármaco consiste no uso de sistemas matriciais. No presente trabalho investigou-se a possibilidade do uso da caseína e acilderivados desta proteína como materiais formadores de matriz, verificando-se a influência da acilaçÝo e compressÝo em algumas propriedades físico-químicas dos sistemas matriciais obtidos. a caseína foi acilada com cinco reagentes fornecedores de grupamentos acil: ácidos cítrico, tartárico e láctico e anidridos acético e succínico. Comprimidos matriciais foram obtidos utilizando-se a caseína nÝo modificada e caseína modificada por acilaçÝo, mediante compressÝo direta, com forças correspondentes a 1,5; 3,0 e 6,0 toneladas métricas/'cm POT. 2'. Os sistemas obtidos foram avaliados com relaçÝo ao perfil de deformaçÝo, friabilidade, perfil de absorçÝo de água e liberaçÝo in vitro. Os ensaios in vitro foram conduzidos nos sucos gástrico e entérico artificiais, empregando o paracetamol como fármaco modelo. A acilaçÝo causou alteraçSes significativas nos perfis de absorçÝo de água, deformaçÝo e liberaçÝo in vitro dos sistemas matriciais comparados com aqueles preparados com a caseína nÝo modificada. Os perfis de absorçÝo de água e liberaçÝo in vitro dos sistemas matriciais comparados com aqueles preparados com a caseína nÝo modificada. Os perfis de absorçÝo de água e liberaçÝo in vitro mostraram a influência da natureza hidrofílica/hidrofóbica dos grupamentos introduzidos na caseína. As caseínas aciladas com anidrido acético e succínico induziram a um menor perfil de absorçÝo de água e, as caseínas mais polares (cítrica, tartárica e láctica) induziram a uma maior absorçÝo. O perfil de liberaçÝo in vitro foi maior para as matrizes hidrofílicas do que para as hidrofóbicas. A introduçào de grupamentos acético e succínio a uma força de compactaçÝo correspondente à 3,0 t/'cm POT. 2', sustentaram a liberaçÝo do fármaco modelo por um período de oito horas nos sucos gástrico e entérico artificiais. A introduçÝo de radicais aniônicos menos hidrofílicos na macromolécula, notadamente o succínio e o acético, podem contribuir para a obtençÝo de um sistema de liberaçÝo prolongada, desde que obtidos em condiçSes adequadas de secagem e compactaçÝo

Validación retrospectiva de tabletas / Retrospective validation of tablets

En industria farmacéutica, la exigencia de un control de calidad riguroso y profundo está orientado a que un producto sea seguro y efectivo, lo cual está ligado a factores económicos, éticos y legales. Para lograr su objetivo se basan en conceptos muy importantes que son las buenas practicas de manufacturas dentro del cual se encuentra la validación; uno de los procedimientos actuales para la comprobación de que los procesos se efectúan con la total confiabilidad, es decir, que un proceso se encuentra controlado. En un inicio, sólo se implementó para técnicas analíticas, pero en la actualidad se aplica también a procesos. La validación de proceso, consiste esencialmente en el control sistemático y documentado de las etapas de trabajo durante la producción de medicamentos, con el fin de garantizar la calidad de un producto y que se cumple estrictamente los procedimientos de fabricación y control establecidos. Todo proceso de validación debe iniciarse con la elaboración de un protocolo de validación donde se especifique las etapas críticas a validar, el procedimiento, los propósitos de la validación, incluyendo la cualificación de grupos como del personal y las especificaciones del producto.

Desenvolvimento de formulaçöes de comprimidos inertes para veicular medicamentos homeopáticos / Development of inert tablet's formulations to incorporate homeopatic medicines

Formulaçöes de comprimidos inertes foram desenvolvidas com a finalidade de se obter formas sólidas para veicular medicamentos homeopáticos. Para tanto, estes devem apresentar comportamento uniforme durante as fases de compressäo e embebiçäo, além de dissolverem-se na boca de forma homogênea e agradável. Foram avaliadas as reologias dos pós e granulados (medidas de ângulo de repouso, densidade aparente e compressibilidade) e as características físicas dos comprimidos (friabilidade, variaçäo de peso médio, dureza e tempo de desintegraçäo). Os comprimidos, de formato lenticular, com 200 mg de peso unitário, foram formulados a partir de lactose (diluente), goma de amido ou xarope simples (aglutinante) e amido em pó (desagregante e lubrificante). Aos granulados foi adicionado estearato de magnésio (lubrificante) e observada a variaçäo de comportamento. A formulaçäo mais adequada continha 90 por cento de lactose, 7,5 por cento de xarope simples, 2,5 por cento de amido em pó e 0,5 por cento de estearato de magnésio.

Recubrimiento pelicular con una dispersión de resinas acrílicas / Pelicular recover with acrilic resin

El presente trabajo se realizó con el propósito de comprobar la conveniencia de la aplicación de resinas acrílicas en medio acuoso para recubrir tabletas, empleándose 2 tipos de tabletas, oblangos y ovaladas a los que se aplicaron 2 tipos de resinas acrílicas, una para cubierta entérica y otra para liberación a nivel del estómago ensayándose diversos espesores de película y cantidades diferentes de materiales hidrófilos de modo que se pudiera definir un menor tiempo de liberación acorde al pH del tracto gastrointestinal. La aplicación de las resinas acrílicas se efectuó empleando un bombo grageador piloto, al cual se adaptó un ventilador de aire frio, una secadora y una pistola de aire comprimido, con una sola tobesa manteniéndose, para la pulverización de las resinas, condiciones definidas de ángulo y velocidad de rodamiento de las tabletas, el ángulo de inclinación de la aguja inyectora y la temperatura de aire de secado. Las tabletas ovaladas fueron más fáciles de recubrir en tanto que los oblangas demandaron de una mayor velocidad de rodamiento para evitar que se pegasen entre si.