Extended release matrix pellets: preparation and compression into disintegrating tablet

The study involves a newer approach of compression of matrix pellets into disintegrating tablet to overcome the rupture of polymer coat during compression of reservoir type pellets. Matrix pellets containing Sodium alginate (Kelton LV CR) at a level of 10, 20 and 30 %w/w was prepared by extrusion/spheronization technique. Sertraline hydrochloride was used as model drug and in vitro release profile of 12 h was targeted. Calcium chloride was used either by granulating the sodium alginate containing blend with 10% w/w solution or by pouring the wet pellets into saturated solution of calcium chloride. Tablets containing pellets were prepared by direct compression process. Acceptance value was used employed to evaluate the uniformity of drug content. In vitro drug release from alginate containing pellets was complete within 4 h and the desired release profile could be achieved only from pellets treated with calcium chloride. The drug release from the uncompressed pellet and compressed tablet was identical, as each pellet was behaving like a monolithic mini matrix system. Scanning electron micrographs of the tablet indicated the uniform distribution of the pellets within the diluent blend. Scanning electron micrographs of the pellets obtained after completion the dissolution test were found to be left with empty sac like structure releasing the drug indicating anomalous type drug release.Matrix pellets containing sodium alginate could be prepared by extrusion spheronization technique which can be an alternative approach in preparing disintegrating tablets from pellets.Keywords: Extrusion/spheronization, Matrix pellets, Acceptance value, MUPS Tablets

Compression and evaluation of extended release matrix pellets prepared by the extrusion/spheronization process into disintegrating tablets

Nesse trabalho, estudou-se nova abordagem para a compressão de matrizes de péletes em comprimidos desintegrantes, com o intuito de resolver os problemas relativos à ruptura do polímero de revestimento durante a compressão dos péletes do tipo reservatório. Matrizes de péletes de liberação estendida foram preparadas pela técnica de extrusão/esferonização, utilizando dispersões aquosas comercialmente disponíveis de etil celulose, polímeros acrílicos e alginato de sódio a 10%, 20% e 30% p/p. O cloridrato de sertralina foi utilizado como fármaco modelo e focalizou-se no perfil de liberação in vitro de 12 horas. Os comprimidos contendo matrizes de péletes foram preparados pelo processo de compressão direta. O valor de aceitação, teste farmacopéico, foi aplicado para estudar a uniformidade de distribuição do fármaco. O efeito da força de compressão (2-6 kN), o tamanho da abertura de extrusão, a composição da mistura diluente, a porcentagem de pélete na liberação de fármaco e o valor de aceitação foram estudados. Como o polímero é uniformemente distribuído dentro de cada pélete, o padrão de liberação do fármaco dos péletes não-comprimidos foi comparável àquele dos comprimidos. As mudanças morfológicas da superfície devidas ao tratamento com cloreto de cálcio foram observadas utilizando-se a microscopia eletrônica de varredura. O pélete segregado da superfície do comprimido mostrou-se plano em direção à força de compressão aplicada com menores deformidades. Em conclusão, os péletes matriz podem se constituir em abordagem alternativa para péletes do tipo reservatório na obtenção de comprimidos desintegrantes para fármacos de liberação estendida.In this study, a novel approach for compression of matrix pellets into disintegrating tablets has been studied in an attempt to overcome the issues pertaining to rupture of polymer coat during compression of reservoir-type pellets. Extended release matrix pellets were prepared by the extrusion/spheronization technique using commercially available aqueous dispersions of ethyl cellulose, acrylic polymers and sodium alginate at 10%, 20% and 30%w/w levels. Sertraline hydrochloride was used as the model drug and an in vitro release profile of 12 h was targeted. Tablets containing matrix pellets were prepared by the direct compression process. Acceptance Value, a pharmacopeial test, was applied to study the uniformity of drug distribution. Effect of compression force (2-6 kN), extrusion screen aperture size, diluent blend composition and pellet percentage on drug release and acceptance value were studied. As polymer is uniformly distributed within each pellet, the drug release pattern from uncompressed pellets was comparable to compressed tablets. Surface morphological changes due to calcium chloride treatment were observed using Scanning electron microscopy. The pellet segregated from the surface of the tablet was found to be flattened in the direction of applied compression force with minor deformities. In conclusion, matrix pellets can constitute an alternative approach to reservoir-type pellets in obtaining disintegrating tablets for extended delivery of drugs

Dilution Phenomenon in Mixed Surfactant based Self Micro Emulsifying Formulations Of Ginger Oleoresin: Ex Vivo And In Vivo Performances

Abstract: Aqueous solubilization of Ginger Oleoresin (GO) in pseudo self micro emulsifying carrier and its influence on ex-vivo intestinal permeation and in-vivo performances was investigated. GO pre-concentrates was prepared using surfactants, Tween 80, Tween 20 and/or 1:1 mixture with a co-surfactant propylene glycol at S/Cos ratio 1:1. Aqueous dilutable region of GO in single or mixed surfactant systems was located from ternary phase diagram drawn between ternary components consisted of surfactant/co-surfactant ratio at 1:1, GO and aqueous phase. Various microstructures were characterized across the dilution line using conductometric and rheological method. Three formulations were selected across the dilution line from mixed surfactants phase diagram as microemulsion area was found to be larger in mixed surfactants over single surfactant based ternary system. GO SMEDDS formulations were physically characterized for refractive index, pH, droplet size and stability assessment. The permeability of GO in diluted pre-concentrate was determined across ex vivo rat intestinal method. Two fold enhancement (p<0.01) in intestinal permeability of GO was obtained from SMEDDS formulation  when diluted upto 9.0ml in comparison to under diluted (2 ml) or over-diluted (25 ml) and control formulation (GO in Tween 80). These findings strongly suggested that SMEDDS diluted upto 9ml behave like a pseudo self emulsifying carrier which inherently had microemulsion characteristics (droplet size 122nm). Modulation of intestinal permeability upon dilution was found closely related with dynamics of microemulsion system. Dilution mediated transitions in microstructure of GO SMEDDS was associated with the changes in the orientation of surfactant molecules at the oil-water interface of microstructures during solubilization of GO. In vivo studies revealed that orally administered GO preconcentrate produced 1.6 folds enhancement in oral bioavailability of GO  over control. Present study demonstrates that intestinal permeability and oral bioavailability can be modulated via exploration of fully dilutable pre-concentrate GO system which could be a possible carrier to enhance oral bioavailability of GO

Dilution Phenomenon in Mixed Surfactant based Self Micro Emulsifying Formulations Of Ginger Oleoresin: Ex Vivo And In Vivo Performances

Abstract: Aqueous solubilization of Ginger Oleoresin (GO) in pseudo self micro emulsifying carrier and its influence on ex-vivo intestinal permeation and in-vivo performances was investigated. GO pre-concentrates was prepared using surfactants, Tween 80, Tween 20 and/or 1:1 mixture with a co-surfactant propylene glycol at S/Cos ratio 1:1. Aqueous dilutable region of GO in single or mixed surfactant systems was located from ternary phase diagram drawn between ternary components consisted of surfactant/co-surfactant ratio at 1:1, GO and aqueous phase. Various microstructures were characterized across the dilution line using conductometric and rheological method. Three formulations were selected across the dilution line from mixed surfactants phase diagram as microemulsion area was found to be larger in mixed surfactants over single surfactant based ternary system. GO SMEDDS formulations were physically characterized for refractive index, pH, droplet size and stability assessment. The permeability of GO in diluted pre-concentrate was determined across ex vivo rat intestinal method. Two fold enhancement (p<0.01) in intestinal permeability of GO was obtained from SMEDDS formulation  when diluted upto 9.0ml in comparison to under diluted (2 ml) or over-diluted (25 ml) and control formulation (GO in Tween 80). These findings strongly suggested that SMEDDS diluted upto 9ml behave like a pseudo self emulsifying carrier which inherently had microemulsion characteristics (droplet size 122nm). Modulation of intestinal permeability upon dilution was found closely related with dynamics of microemulsion system. Dilution mediated transitions in microstructure of GO SMEDDS was associated with the changes in the orientation of surfactant molecules at the oil-water interface of microstructures during solubilization of GO. In vivo studies revealed that orally administered GO preconcentrate produced 1.6 folds enhancement in oral bioavailability of GO  over control. Present study demonstrates that intestinal permeability and oral bioavailability can be modulated via exploration of fully dilutable pre-concentrate GO system which could be a possible carrier to enhance oral bioavailability of GO

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

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.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

Arformoterol Tartrate: A Review of Pharmacology, Analysis and Clinical Studies

This article is a review of the therapeutic significance of arformoterol tartrate, a new generation 2 adrenergic agonist bronchodilator available in a nebulized form. Arformoterol is well absorbed through the lungs when administered via a standard jet nebulizer and is useful in long-term maintenance therapy of bronchoconstriction in chronic obstructive pulmonary disease (COPD). Much clinical evidence suggest the potentially enhanced efficacy of this drug in the treatment of COPD including chronic bronchitis and emphysema. Various hyphenated analytical methodologies have also been employed for the determination and quantification of arformoterol. This review provides an updated account on the pharmacology, pharmacokinetics, clinical studies, analytical techniques, drug-drug interactions, contraindications, and therapeutic applications of arformoterol tartrate.Keywords: Arformoterol tartrate, Adrenergic agonist, Bronchodilator, COPDTropical Journal of Pharmaceutical Research December 2010; 9 (6): 595-60

Pre-Formulation Study for Palatable Microbeads of Lycopene

Lycopene is a widely used nutraceuticals for its antioxidant property but the molecule has poor aqueous solubility, high instability, and extremely low intestinal permeability leading to its poor bioavailability. In the present study, pre-formulation study was carried out to prepare sodium alginate microbeads with the intention to deliver an effective amount of lycopene for high absorption through oral route. A thorough physical characterization and spectral analysis were done to understand the characteristic of lycopene such as its melting point, UV spectrophotometric analysis, chromatography through reverse phase HPLC. Fourier transform infrared spectroscopy and differential scanning calorimetry were adopted to know the interaction of sodium alginate with lycopene. Box-Behnken design (version 9.0.2.0, Stat Ease Inc, USA) was used to analyse the effect of formulation variables such as sodium alginate (%), glutaraldehyde (%) and stirring speed on lycopene entrapment and its loading into microbeads. The adopted preformulation strategy revealed that lycopene was a crystalline powder with a sharp melting point at 155oC and the prominent functional groups were present in the sample. UV and HPLC analysis revealed precise quantitation and authenticity of lycopene. Excipient compatibility also revealed inertness of sodium alginate. Response surface morphology revealed significant effect of alginate, glutaraldehyde and stirring speed on formation of best composition. Therefore, it is concluded that lycopene can be formulated as microbeads for oral drug delivery. Keywords: lycopene, sodium alginate, permeation, absorption, microbead

Nanostructured Lipid Carrier-Based Codelivery of Raloxifene and Naringin: Formulation, Optimization, In Vitro, Ex Vivo, In Vivo Assessment, and Acute Toxicity Studies

This work aimed to develop dual drug-loaded nanostructured lipid carriers of raloxifene and naringin (RLX/NRG NLCs) for breast cancer. RLX/NRG NLCs were prepared using Compritol 888 ATO and oleic acid using a hot homogenization−sonication method and optimized using central composite design (CCD). The optimized RLX/NRG NLCs were characterized and evaluated using multiple technological means. The optimized RLX/NRG NLCs exhibited a particle size of 137.12 nm, polydispersity index (PDI) of 0.266, zeta potential (ZP) of 25.9 mV, and entrapment efficiency (EE) of 91.05% (raloxifene) and 85.07% (naringin), respectively. In vitro release (81 ± 2.2% from RLX/NRG NLCs and 31 ± 1.9% from the RLX/NRG suspension for RLX and 93 ± 1.5% from RLX/NRG NLCs and 38 ± 2.01% from the RLX/NRG suspension for NRG within 24 h). Concurrently, an ex vivo permeation study exhibited nearly 2.3 and 2.1-fold improvement in the permeability profiles of RLX and NRG from RLX/NRG NLCs vis-à-vis the RLX/NRG suspension. The depth of permeation was proved with CLSM images which revealed significant permeation of the drug from the RLX/NRG NLCs formulation, 3.5-fold across the intestine, as compared with the RLX/NRG suspension. An in vitro DPPH antioxidant study displayed a better antioxidant potential of RLX/NRG in comparison to RLX and NRG alone due to the synergistic antioxidant effect of RLX and NRG. An acute toxicity study in Wistar rats showed the safety profile of the prepared nanoformulations and their excipients. Our findings shed new light on how poorly soluble and poorly permeable medicines can be codelivered using NLCs in an oral nanoformulation to improve their medicinal performance

Updating the approaches to define susceptibility and resistance to anti-tuberculosis agents: implications for diagnosis and treatment

11 páginas, 2 figuras, 1 tablaInappropriately high breakpoints have resulted in systematic false-susceptible AST results to anti-TB drugs. MIC, PK/PD and clinical outcome data should be combined when setting breakpoints to minimise the emergence and spread of antimicrobial resistance.I. Comas was supported by PID2019-104477RB-I00 from the Spanish Science Ministry and by ERC (CoG 101001038)Peer reviewe