Preparation and characterization of cefuroxime axetil solid dispersions using hydrophilic carriers.

AIM: The objective of the current study is to increase the dissolution rate of cefuroxime axetil (CA) by formation of binary CA solid dispersion using water soluble carriers such as polyvinylpyrrolidone (PVP K30) and polyethylene glycol (PEG 4000). METHODS: Solid dispersions (SDs) between CA and PVP K30/PEG 4000 were formed by dissolving both compounds in a common solvent, methanol, which were rotary evaporated at 40°C for 12 h. Physical mixtures between CA and PVP K30/PEG 4000 were also formulated as to compare the efficiency of SDs. The physicochemical properties of CA and all its formulations were then characterized using differential scanning calorimetric analysis (DSC), powder X-ray diffraction studies (PXRD), and Fourier transform infrared spectroscopy (FTIR). RESULTS: All SD formulations were found to have a higher dissolution rate comparatively to pure CA, while only physical mixtures of PVP K30 were found having a significantly higher dissolution rate. The enhancement of dissolution rate SD by PVP K30 may be caused by increase wettability, solubility, reduction in particle size or the formation of CA ß crystalline. Increment of dissolution rate of CA SDs by PEG 4000 similarly may be caused by increase wettability, solubility, and reduction in particle size. This phenomenon may also be caused by amorphization as suggested by DSC and PXRD. CONCLUSIONS: The SD of CA with PVP K30 and PEG 4000, lends an ample credence for better therapeutic efficacy.

Formulation and optimization of gastric floating drug delivery system using Central composite design and its biopharmaceutical evaluation.

The present work investigates the formulation and biopharmaceutical estimation of gastric floating drug delivery system (GFDDS) of propranolol HCl using semi-synthetic polymer carboxymethyl ethyl cellulose (CMEC) and a synthetic polymer polyethylene oxide (PEO). A central composite design was applied for optimization of polymer quantity (CMEC or PEO) and sodium bicarbonate concentration as independent variables. The dependent variables evaluated were: % of drug release at 1 hr (D1hr), % drug release at 3 hr (D3hr) and time taken for 95% of drug release (t95). Numerical optimization and graphical optimization were conducted to optimize the response variables. All observed responses of statistically optimized formulations were in high treaty with predicted values. Accelerated stability studies were conducted on the optimized formulations at 40 ± 2°C/75% ± 5% RH and confirm that formulations were stable. Optimized formulations were evaluated for in vivo buoyancy characterization in human volunteers and were found buoyant in gastric fluid. Gastric residence time was enhanced in the fed but not the fasted state. The optimized formulations and marketed formulation were administered to healthy human volunteers and evaluated for pharmacokinetic parameters. Mean residence time (MRT) was prolonged and AUC levels were increased for both optimized floating tablets when compared with marketed product. High relative bioavailability obtained with optimized gastric floating tablets compared to commercial formulation, indicated the improvement of bioavailability.

Preparation and in vitro characterization of a non-effervescent floating drug delivery system for poorly soluble drug, glipizide.

The aim of the present study was to formulate a non-effervescent floating drug delivery system of glipizide, a poorly water soluble drug. The solubility of glipizide was initially enhanced using a solid dispersion (SD) strategy with the help of hydrophilic carriers such as poloxamer, cyclodextrin, and povidone. The optimized core material/SD was further formulated into non-effervescent floating tablets (NEFT) by using matrix ballooning inducers, such as crospovidone and release retarding agents including HPMC and PEO. Poloxamer-based solid dispersions prepared by a solvent evaporation technique showed the highest dissolution rate (1 : 10 drug to carrier ratio) compared with all other dispersions. NEFT were evaluated for all physico-chemical properties including in vitro buoyancy, dissolution, and release rate. All of the tablets were found to be within pharmacopoeial limits and all of the formulations exhibited good floating behavior. The formulations (F2 and F3) were optimized based on their 12 h drug retardation with continuous buoyancy. The optimized formulations were characterized using FTIR and DSC and no drug and excipient interaction was found. In-vitro buoyancy and dissolution studies showed that non-effervescent floating drug delivery systems provide a promising method of achieving prolonged gastric retention time and improved bioavailability of glipizide.

Characterization and solubility study of norfloxacin-polyethylene glycol, polyvinylpyrrolidone and carbopol 974p solid dispersions.

OBJECTIVE: Norfloxacin has a low aqueous solubility which leads to poor dissolution. Keeping this fact in mind the purpose of the present study is to formulate and evaluate norfloxacin solid dispersion. METHODS: Solid dispersions were prepared using hydrophilic carriers like polyethylene glycol (PEG) 4000, polyvinylpyrrolidone (PVP) k30 and carbopol 974pNF (CP) in various ratios using solvent evaporation technique. These formulations were evaluated using solubility studies, dissolution studies; Fourier transmitted infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetery (DSC). The influence of polymer type and drug to polymer ratio on the solubility and dissolution rate of norfloxacin was also evaluated. RESULTS: FTIR analysis showed no interaction of all three polymers with norfloxacin. The results from XRD and DSC analyses of the solid dispersion preparations showed that norfloxacin existsin its amorphous form. Among the Norfloxacin: PEG solid dispersions, Norfloxacin: PEG 1:14 ratio showed the highest dissolution rate at pH 6.8. For norfloxacin: PVP solid dispersions, norfloxacin: PVP 1:10 ratio showed the highest dissolution rate at pH 6.8. For Norfloxacin: CP solid dispersions, norfloxacin: P 1:2 ratio showed the highest dissolution rate at pH 6.8. CONCLUSION: The solid dispersion of norfloxacin with polyethylene glycol (PEG) 4000, polyvinylpyrrolidone (PVP) k30 and carbopol 974p NF (CP), lends an ample credence for better therapeutic efficacy.

Preparation and in vitro characterization of non-effervescent floating drug delivery system of poorly soluble drug, carvedilol phosphate.

The objective of the study was to enhance the solubility of carvedilol phosphate and to formulate it into non-effervescent floating tablets using swellable polymers. Solid dispersions (SD) of carvedilol were prepared with hydrophilic carriers such as polyvinylpyrrolidone and poloxamer to enhance solubility. Non-effervescent floating tablets were prepared with a combination of optimized solid dispersions and release retarding polymers/swellable polymers such as xanthan gum and polyethylene oxide. Tablets were evaluated for physicochemical properties such as hardness, thickness and buoyancy. SD prepared with the drug to poloxamer ratio of 1:4 by melt granulation showed a higher dissolution rate than all other dispersions. Formulations containing 40 mg of polyethylene oxide (C-P40) and 50 mg xanthan gum (C-X50) were found to be best, with the drug retardation up to 12 hours. Optimized formulations were characterized using FTIR and DSC and no drug and excipient interactions were detected.

Design and evaluation of a gastroretentive drug delivery system for metformin HCl using synthetic and semi-synthetic polymers / Diseño y evaluación de un sistema gastro-retentivo de administración de metformina HCl, utilizando polímeros sintéticos y semisintéticos

The aim of the present research was to prepare and evaluate a gastroretentive drug delivery system for metformin HCl, using synthetic and semi-synthetic polymers. The floating approach was applied for preparing gastroretentive tablets (GRT) and these tablets were manufactured by the direct compression method. The drug delivery system comprises of synthetic and semi-synthetic polymers such as polyethylene oxide and Carboxymethyl ethyl cellulose (CMEC) as release-retarding polymers. GRT were evaluated for physico-chemical properties like weight variation, hardness, assay friability, in vitro floating behaviour, swelling studies, in vitro dissolution studies and rate order kinetics. Based upon the drug release and floating properties, two formulations (MP04 & MC03) were selected as optimized formulations. The optimized formulations MP04 and MC03 followed zero order rate kinetics, with non-Fickian diffusion and first order rate kinetics with erosion mechanism, respectively. The optimized formulation was characterised with FTIR studies and it was observed that there was no interaction between the drug and polymers.

El objetivo del presente trabajo consistió en preparar y evaluar un sistema de administración gastro-retentivo de metformina HCl, utilizando polímeros sintéticos y semisintéticos. Se aplicó el método de flotación para la elaboración de los comprimidos de retención gástrica (CRG) y éstos se prepararon mediante el método de compresión directa. El sistema de suministro del fármaco estaba constituido por polímeros sintéticos y semisintéticos, tales como el óxido de polietileno y la carboximetil etil celulosa, como agentes retardadores de la liberación del fármaco. Se evaluaron las propiedades físico-químicas de los CRG, tales como: variación de peso, dureza, friabilidad, comportamiento flotante in vitro, capacidad de inflación, estudios de disolución in vitro y su tasa de orden cinético. Se seleccionaron dos fórmulas (MP04 y MC03), sobre la base de la liberación del fármaco y las propiedades de flotabilidad, como fórmulas óptimas. Estas fórmulas MP04 y MC03 optimizadas siguieron cinéticas de velocidad de orden cero, con difusión no-Fickian y tasa cinética de primer orden con mecanismo de erosión, respectivamente. Las fórmulas óptimas se caracterizaron con estudios FTIR y se observó que no hubo interacción entre el fármaco y los polímeros.

Development of solid dispersion systems of dapivirine to enhance its solubility.

Dapivirine, formerly known as TMC 120, is a poorly-water soluble anti-HIV drug, currently being developed as a vaginal microbicide. The clinical use of this drug has been limited due to its poor solubility. The aim of this study was to design solid dispersion systems of Dapivirine to improve its solubility. Solid dispersions were prepared by solvent and fusion methods. Dapivirine release from the solid dispersion system was determined by conducting in-vitro dissolution studies. The physicochemical characteristics of the drug and its formulation were studied using Differential Scanning Calorimetry (DSC), powder X-ray Diffraction (XRD), Fourier-transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). A significant improvement in drug dissolution rate was observed with the solid dispersion systems. XRD, SEM and DSC results indicated the transformation of pure Dapivirine which exists in crystalline form into an amorphous form in selected solid dispersion formulations. FTIR and HPLC analysis confirmed the absence of drug-excipient interactions. Solid dispersion systems can be used to improve the dissolution rate of Dapivirine. This improvement could be attributed to the reduction or absence of drug crystallinity, existence of drug particles in an amorphous form and improved wettability of the drug.

Anti-inflammatory, antibacterial and analgesic potential of cocos nucifera linn.: a review.

At present, approximately 25%of drugs in modern pharmacopoeia are derived from plant sources (phytomedicines) that can be developed for the treatment of diseases and disorders. Many other drugs are synthetic analogues built on the prototype compounds isolated from plants. Cocos nucifera Linn. (Arecaceae), which is commonly known as coconut, is a plant possessing a lot of potential as an ingredient in traditional medicines for the treatment of metabolic disorders and particularly as an anti-inflammatory, antimicrobial and analgesic agent. This review emphasizes on the recent literature and research findings that highlight the significant biological activities of C. nucifera Linn. such as its anti-inflammatory, antimicrobial and analgesic properties. This review can help researchers keen on exploiting the therapeutic potential of C. nucifera Linn. which may motivate them to further explore their commercial viability.

Comportamiento de la disolución de aceclofenaco-PVP coprecipitados / Dissolution behaviour of aceclofenac-PVP coprecipitates

Objetivo: El objetivo de esta investigación fue estudiar el efecto del PVP en la disolución in vitro del aceclofenaco en coprecipitados. Material y métodos: Se prepararon diferentes coprecipitados de aceclofenaco con distintas cargas de droga y se llevaron a cabo los estudios in vitro de disolución de la droga pura, mezclas físicas y coprecipitados. Resultados: Los coprecipitados de aceclofenaco con PVP mostraron un considerable incremento de la tasa de disolución en comparación con las mezclas físicas y la droga pura en HCl 0,1 N y tampón fosfato con pH 7,4. Los coprecipitados con proporción 1:2 mostraron una tasa máxima de disolución en comparación con otras proporciones. La naturaleza amorfa de la droga en coprecipitados fue confirmada con microscopia electrónica de barrido así cómo el descenso de la entalpia de fusión de los coprecipitados con respecto a la droga pura. Los estudios de espectrometría FT-IR y calorimetría diferencial de barrido indicaron que no hubo interacción entre el aceclofenaco y el PVP en estado sólido. La mejora de la disolución se atribuyó al descenso de la cristalinidad y humedad de la droga, la formación del eutéctico y el efecto solubilizante del soporte de los coprecipitados de aceclofenaco. Conclusión: La disolución del aceclofenaco puede ser mejorada con el uso de los soportes hidrófílicos como el PVP(AU)

Aim: The objective of the present investigation was to study the effect of PVP on in vitro dissolution of aceclofenac from coprecipitates. Materials and Methods: Aceclofenac coprecipitates (CP) with different drug loadings were prepared and in vitro dissolution studies of pure drug, physical mixtures and coprecipitates were carried out. Results: Coprecipitates of aceclofenac with PVP showed considerable increase in the dissolution rate in comparison with physical mixture and pure drug in 0.1 N HCl, pH1.2 and phosphate buffer, pH, 7.4. Coprecipitates in 1:2 ratio showed maximum dissolution rate in comparison to other ratios. Amorphous nature of the drug in coprecipitates was confirmed by scanning electron microscopy and a decrease in enthalpy of drug melting in coprecipitates compared to the pure drug. FT-IR spectroscopy and differential scanning calorimetry studies indicated no interaction between aceclofenac and PVP in coprecipitates in solid state. Dissolution enhancement was attributed to decreased crystallinity of the drug and to the wetting, eutectic formation and solubilizing effect of the carrier from the coprecipitates of aceclofenac. Conclusion: dissolution of aceclofenac can be enhanced by the use of hydrophilic carriers like PVP(AU)

Resistoflavine, cytotoxic compound from a marine actinomycete, Streptomyces chibaensis AUBN1/7.

In our systematic screening programme for marine actinomycetes, a bioactive Streptomycete was isolated from marine sediment samples of Bay of Bengal, India. The taxonomic studies indicated that the isolate belongs to Streptomyces chibaensis and it was designated as S. chibaensis AUBN1/7. The isolate yielded a cytotoxic compound. It was obtained by solvent extraction followed by the chromatographic purification. Based on the spectral data of the pure compound, it was identified as quinone-related antibiotic, resistoflavine (1). It showed a potent cytotoxic activity against cell lines viz. HMO2 (Gastric adenocarcinoma) and HePG2 (Hepatic carcinoma) in vitro and also exhibited weak antibacterial activities against Gram-positive and Gram-negative bacteria.

1-Hydroxy-1-norresistomycin, a new cytotoxic compound from a marine actinomycete, Streptomyces chibaensis AUBN1/7.

In our systematic screening programme for marine actinomycetes, a bioactive streptomycete was isolated from marine sediment samples of the Bay of Bengal, India. The isolate yielded a new cytotoxic compound. This was obtained by solvent extraction followed by chromatographic purification. The pure compound was identified from spectroscopic data as a quinone-related antibiotic, 1-hydroxy-1-norresistomycin (1). It showed a potent cytotoxic activity against cell lines viz. HMO2 (gastric adenocarcinoma) and HePG2 (hepatic carcinoma) in vitro. It also exhibited antibacterial activities against Gram-positive and Gram-negative bacteria.