Novel Thermosensitive and Mucoadhesive Nasal Hydrogel Containing 5-MeO-DMT Optimized Using Box-Behnken Experimental Design.

We present the development and characterization of a nasal drug delivery system comprised of a thermosensitive mucoadhesive hydrogel based on a mixture of the polymers Poloxamer 407, Poloxamer 188 and Hydroxypropyl-methylcellulose, and the psychedelic drug 5-methoxy-N,-N-dimethyltryptamine. The development relied on a 3 × 3 Box-Behnken experimental design, focusing on optimizing gelification temperature, viscosity and mucoadhesion. The primary objective of this work was to tailor the formulation for efficient nasal drug delivery. This would increase contact time between the hydrogel and the mucosa while preserving normal ciliary functioning. Following optimization, the final formulation underwent characterization through an examination of the in vitro drug release profile via dialysis under sink conditions. Additionally, homogeneity of its composition was assessed using Raman Confocal Spectroscopy. The results demonstrate complete mixing of drug and polymers within the hydrogel matrix. Furthermore, the formulation exhibits sustained release profile, with 73.76% of the drug being delivered after 5 h in vitro. This will enable future studies to assess the possibility of using this formulation to treat certain mental disorders. We have successfully developed a promising thermosensitive and mucoadhesive hydrogel with a gelling temperature of around 32 °C, a viscosity close to 100 mPas and a mucoadhesion of nearly 4.20 N·m.

Starch-based films affected by the addition of collagen from Prochilodus magdalenae residues and HPMC: Application in Andean blackberry (Rubus glaucus Benth) coatings.

Starch-based films offer the advantages of biodegradability, edibility, barrier properties, flexibility, and adaptability. This study compared the physicochemical properties of starch-based films by adding raw fish collagen and hydroxypropylmethylcellulose (HPMC). The tensile properties were evaluated, and the interaction with water was analyzed. Barrier properties, such as water vapor and oxygen permeability, were examined, and optical properties, such as gloss and good internal transmittance, were evaluated. The films were evaluated as coatings on Andean blackberries (Rubus glaucus Benth) for 2 weeks at 85% RH and 25°C. The results showed that the inclusion of collagen caused a reduction in the tensile strength and elastic modulus of the films. Also, the formulation with the highest collagen concentration (F7) exhibited the lowest weight loss and water vapor permeability, also it had the highest collagen concentration and showed the highest reduction in Xw and WAC, with values of 0.048 and 0.65 g water/g dry film, respectively. According to analyzing the optical properties, F1 presented the highest bright-ness and transmittance values, with 18GU and 82 nm values, respectively. In general, the films and coatings are alternatives to traditional packaging materials to prolong the shelf life of these fruits.

Development of nanostructured environmentally responsive system containing hydroxypropyl methylcellulose for nose-to-brain administration of meloxicam.

The intranasal administration of drugs using environmentally responsive formulations, employing a combination of hydroxypropyl methylcellulose (HPMC) and poloxamer 407 (P407), can result in release systems that may assist in the treatment of neurological diseases. Meloxicam, considered a potential adjuvant in the treatment of Alzheimer's disease, could be used in these platforms. The aim of this work was to develop a mucoadhesive, thermoresponsive, and nanostructured system containing HPMC for nose-to-brain administration of meloxicam. The initially selected systems were investigated for their rheological, mechanical, and micellar size characteristics. The systems were dilatant at 25 °C and pseudoplastic with a yield value at 37 °C, showing viscoelastic properties at both temperatures. The platform containing HPMC (0.1%, w/w) and P407 (17.5%, w/w) was selected and demonstrated good mucoadhesive properties, along with an appropriate in vitro release profile. HPMC could form a binary system with P407, displaying superior mucoadhesive and thermoresponsive properties for nose-to-brain meloxicam administration, indicating that the selected formulation is worthy of clinical studies.

Modified celluloses improve the proofing performance and quality of bread made with a high content of resistant starch.

BACKGROUND: Adding resistant starch (RS) to bread formulations is a promising way of increasing fiber content of white bread. However, the partial replacement of wheat flour (WF) by RS can lead to a decrease in technological quality. The objective of this study was to analyze the performance of hydroxypropylmethylcellulose and carboxymethylcellulose as improvers of wheat bread with a high level of replacement (30%) with maize RS. The levels of the modified celluloses were 1% and 1.5% (WF + RS basis), and a formulation without modified celluloses was used as control. Proofing time, loaf volume, crumb characteristics (porosity, texture), and bread staling parameters (hardness increase, moisture loss), among other attributes, were analyzed, and principal component analysis was applied to compare samples. RESULTS: The use of both modified celluloses was effective in improving the quality of breads. Specific volume and crumb porosity were enhanced, particularly at the 1.5% level. Breads with modified celluloses also allowed a higher retention of water and a better preservation of mechanical properties during storage. The principal component analysis projection graph for the first two principal components showed that samples with modified celluloses were clustered by the level of hydrocolloid addition rather than by the type of hydrocolloid used, although all the samples with modified celluloses were close to each other and distant from the control sample without hydrocolloids. CONCLUSION: The quality decrease resulting from the replacement of WF by a high level of RS can be greatly compensated by the use of structuring agents such as hydroxypropylmethylcellulose and carboxymethylcellulose. © 2022 Society of Chemical Industry.

Sustained release matrix tablet of 100 mg losartan potassium: Formulation development and in vitro characterization

Abstract Sustained release matrix tablets of 100 mg losartan potassium HCl were fabricated with two release retarding polymers namely HPMC K100 M and affinisol by direct compression method. Nine trial formulations were prepared by varying content of these polymers, each from 50 mg to 100 mg; keeping the total weight of the tablet 310 mg. The best formulation was selected based on in vitro drug release profile for 12 hours conducted in Type II dissolution apparatus at 50 rpm and water as dissolution medium. Pre-compression parameters such as bulk density, tap density, Carr's index and Hausner ratio were evaluated for the selected tablet. The tablets were subjected to thickness, weight variation test, drug content, hardness and friability. Drug release kinetics, surface morphology and accelerated stability study were investigated for that selected formulation. Formulation F4 with the composition of 75 mg HPMC K100M and 100 mg affinisol was selected as the best formulation that extended the drug release up to 12 hours. Pre-compression parameters and other tableting properties were within the Pharmacopoeia limit. Release kinetics analysis proved non-fickian zero-order drug release and that was further confirmed by surface morphology of the tablets before and after dissolution study visualized by SEM. The developed formulation was found to be stable for one month stored at 60 ○C.

A comparative physicochemical and pharmacological evaluation of dexamethasone sodium phosphate and betamethasone sodium phosphate mucoadhesive gels for the treatment of oral submucous fibrosis in rats

Abstract The present study is aimed to formulate steroidal oral mucoadhesive gels of dexamethasone sodium phosphate and betamethasone sodium phosphate. Six gel formulations each of dexamethasone sodium phosphate and betamethasone sodium phosphate prepared using two different polymers carboxymethyl cellulose sodium and hydroxypropyl methylcellulose, in variable proportions. All the formulations subjected for assessment of various physicochemical parameters and mechanical properties. The formulations BSP5 and DSP5, both containing 1.25 % carboxymethyl cellulose sodium, 1.25 % hydroxypropyl methylcellulose, exhibiting mucoadhesive strength of 12.300 ± 0.004 and 12.600 ± 0.01, adhesiveness of 28.04 ± 00 and 30.02 ± 00, cohesiveness of 28.04 ± 00 and 30.02 ± 00, drug release of 86.869 ± 0.380 % and 88.473 ± 0.457 % respectively were considered as promising ones and were further subjected for stability studies and in vivo study in male albino rats. Formulation DSP5 upon oral application for 4 months in arecoline induced oral submucous fibrosis rats, showed more than 80 % reduction in fibrosis as compared with BSP5 which showed nearly 50 % reduction. These results were concluded on the basis of histopathological profile and weight gain among the experimental animals during in vivo study. Hence, DSP5 by minimizing the painful injuries and morbidities justifies being suitable noninvasive model for OSMF treatment.

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.

Conservation of 'Palmer' mango with an edible coating of hydroxypropyl methylcellulose and beeswax.

Mango is a tropical fruit presenting intense postharvest metabolism. In storage at room temperature, it presents a short shelf life due to the high respiratory rate, and consequent ripening, which limits the marketing period in distant regions. This study evaluated the effect of edible coatings of hydroxypropyl methylcellulose and beeswax in concentrations of 10, 20, and 40% in 'Palmer' mangoes stored for 15 days at 21 °C. The coatings controlled ripening, maintaining peel and pulp colors, firmness, soluble solids (SS), titratable acidity (TA), SS/TA ratio, sugars, ascorbic acid, phenolic compounds, flavonoids, ß-carotene, and antioxidant activity. Also, they reduced weight loss, oxidative stress, and the anthracnose (Colletotrichum gloeosporioides) incidence, without inducing alcohol dehydrogenase activity, which suggests that coated fruit did not ferment. Treatment with 20% beeswax was the most suitable for industrial applications, increasing in six days the mangoes shelf life.

Polymeric Nanoparticle Associated with Ceftriaxone and Extract of Schinopsis Brasiliensis Engler against Multiresistant Enterobacteria.

Bacterial resistance has become an important public health problem. Bacteria have been acquiring mechanisms to resist the action of antimicrobial active pharmaceutical ingredients (API). Based on this, a promising alternative is the use of nanotechnology, since when the systems are presented in nanometric size, there is an increase in the interaction and concentration of the action at the target site improving the activity. Thus, this study aims to develop a polymeric nanoparticle (PN) composed of chitosan and hydroxypropylmethylcellulose, as an innovative strategy for the administration of an association between ceftriaxone and extract of S. brasiliensis, for the treatment of Enterobacteriaceae. From a Box-Behnken design, nanoparticles were obtained and evaluated using the DLS technique, obtaining the particle size between 440 and 1660 nm, IPD from 0.42 to 0.92, and positive charges. Morphological characteristics of PN by SEM revealed spherical morphology and sizes similar to DLS. Infrared spectroscopy showed no chemical interaction between the components of the formulation. The broth microdilution technique evaluated their antimicrobial activity, and a considerable improvement in the activity of the extract and the API compared to the free compounds was found, reaching an improvement of 133 times in the minimum inhibitory activity CRO.

Development of controlled release dexketoprofen tablets and prediction of drug release using Artificial Neural Network (ANN) modelling

Dexketoprofen trometamol (DT) is an active S (+) enantiomer of ketoprofen, and a non-steroidal anti-inflammatory agent. DT has a short biological half-life and the dosing interval is quite short when there is a need to maintain the desirable effect for longer time periods. Consequently, a controlled release DT tablet was designed for oral administration aiming to minimize the number of doses and the possible side effects. Calculations of the parameters for controlled release DT tablets were shown clearly. Controlled release matrix-type tablet formulations were prepared using hydroxypropyl methylcellulose (HPMC) (low and high viscosity), Eudragit RS and Carbopol, and the effects of different polymers on DT release from the tablet formulations were investigated. The dissolution rate profiles were compared and analyzed kinetically. An Artificial Neural Network (ANN) model was developed to predict drug release and a successful model was obtained. Subsequently, an optimum formulation was selected and evaluated in terms of its analgesic and anti-inflammatory activity. Although the developed controlled release tablets did not have an initial dose, they were found to be as effective as commercially available tablets on the market. Dissolution and in vivo studies have shown that the prepared tablets were able to release DT for longer time periods, making the tablets more effective, convenient and more tolerable.

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 and characterization of lipid-polymeric nanoparticles for oral insulin delivery.

INTRODUCTION: The oral route is widely accepted as the most physiological path for exogenous administration of insulin, as it closely mimic the endogenous insulin pathway. Thus, in this work it is proposed an innovative lipid-polymeric nanocarrier to delivery insulin orally. Areas covered: Nanoparticles were produced through a modified solvent emulsification-evaporation method, using ethyl palmitate and hydroxypropylmethylcellulose acetate succinate as matrix. Lipid-polymeric nanoparticles were around 300 nm in size, negatively charged (-20 mV) and associated insulin with efficiency higher than 80%. Differential scanning calorimetry suggested thermal stability of nanoparticles. In vitro release assays under simulated gastrointestinal conditions resulted in 9% and 14% of insulin released at pH 1.2 during 2 h and at pH 6.8 for 6 h, respectively, demonstrating the ability of those nanoparticles to protect insulin against premature degradation. Importantly, nanoparticles were observed to be safe at potential therapeutic concentrations as did not originate cytotoxicity to intestinal epithelial cells. Lastly, the permeability of nanoencapsulated insulin through Caco-2 monolayers and a triple Caco-2/HT29-MTX/Raji B cell model correlated well with slow release kinetics, and fosters the effectiveness of nanoparticles to promote intestinal absorption of peptidic drugs. Expert opinion: Lipid-polymeric nanoparticles were developed to encapsulate and carry insulin through intestine. Overall, nanoparticles provide insulin stability and intestinal permeability.

Análise comparativa de perfis de dissolução in vitro e in silico de comprimidos de liberação modificada contendo metformina / Comparative analysis of dissolution profiles in vitro and in silico of modified release tablets containing metformin

A dissolução de um fármaco a partir de uma forma farmacêutica (FF) sólida oral é um pré-requisito para que o mesmo seja absorvido pelo organismo e cumpra seus efeitos terapêuticos. O ensaio de dissolução de medicamentos permite avaliar a quantidade de princípio ativo que é liberado a partir de sua FF, mimetizando in vitro o processo que ocorre no trato gastrointestinal (TGI). O DDDPlus® é o único programa de computador dedicado exclusivamente a simular ensaios de dissolução. O objetivo deste trabalho foi avaliar a capacidade do programa de computador DDDPlus® em fornecer perfis de dissolução in silico de comprimidos matriciais contendo metformina semelhantes aos perfis de dissolução in vitro e avaliar a possibilidade de substituir a comparação de perfis de dissolução in vitro de diferentes formulações de comprimidos matriciais contendo metformina pela comparação de perfis de dissolução in silico fornecidos pelo DDDPlus®.Para tanto, um planejamento estatístico foi realizado para obtenção de perfis de dissolução, variando a velocidade das pás e o uso do sinker. Os perfis de dissolução de 3 formulações teste (T1, T2 e T3) de comprimidos de liberação modificada por matriz polimérica contendo metformina foram comparadas pelos métodos de eficiência de dissolução (ED), tempo médio de dissolução (TMD), fator de diferença (f2) e fator de semelhança (f1). Os resultados indicaram o uso do sinker como fator determinante para a ED e TMD. Assim, o método que utilizava o sinker e a velocidade das pás de 50RPM foi utilizado para avaliar 4 produtos comercializados no Brasil. No DDDPlus® os ensaios de dissolução in vitro das formulações T1, T2 e T3 foram otimizadas para a obtenção das constantes de calibração (CC), as CC foram utilizadas para simular os ensaios de dissolução de T1, T2 e T3 em velocidades de 25 e 50RPM. Os perfis de dissolução simulados foram comparados aos perfis observados, resultando em valores de R2. Valores de R2 acima de 0,90 foram obtidos para todas as simulações realizadas utilizando CC de ensaios in vitro que utilizaram sinker, indicando o potencial do programa em auxiliar o desenvolvimento de novas formulações. Valores de R2 abaixo de 0,70 foram obtidos após a simulação de ensaios utilizando CC de ensaios in vitro que não utilizavam o sinker, indicando que o programa de computador não previu a adesão do comprimido ao fundo da cuba de dissolução durante o ensaio. Os perfis de dissolução simulados das formulações T1, T2 e T3 foram comparadas por f1 e f2 com os perfis de dissolução dos produtos do mercado. Tais comparações concluíram que o software não é indicado como substituto dos ensaios in vitro quando se almeja comparar perfis de dissolução

Dissolution of a drug from an oral solid pharmaceutical form (FF) is a prerequisite for it to be absorbed by the body and to fulfill its therapeutic effects. in vitroDrug dissolution assay allows the amount of active principle released from a FF and mimics the in vivo the process that occurs in the gastrointestinal tract (TGI). DDDPlus® is the only computer program dedicated exclusively to simulating dissolution testing. The objective of this work was to evaluate the ability of DDDPlus® software to provide in silico dissolution profiles of matrix tablets containing metformin similar to in vitro dissolution profiles and to evaluate the possibility of replacing in vitro dissolution profiles comparison of different formulations of matrix tablets containing metformin for a comparison of in silico dissolution profiles provided by DDDPlus®. For this purpose, a statistical design was used, varying agitation speed and the use of sinker to obtain dissolution profiles for 3 test formulations (T1, T2 and T3) of polymer matrix-modified release tablets containing metformin. Dissolution profiles were compared by means of dissolution efficiency (ED), mean dissolution time (TMD), difference factor (f2) and similarity factor (f1). The results indicated the use of sinker as a determinant factor for ED and TMD. Thus, the method that used sinker and agitation speed of 50RPM was used to evaluate 4 products commercialized in Brazil. in vitro dissolution tests of the T1, T2 and T3 formulations were optimized using In DDDPlus® to obtain the calibration constants (CC), which were used to simulate dissolution profiles of T1, T2 and T3 at speeds of 25 and 50RPM. in silico dissolution profiles were compared to in vitro dissolution profiles, resulting in R2 values. R2 values above 0.90 were obtained for all simulations performed using CC from in vitro assays using sinker, indicating the potential of the program to assist the development of new formulations. R2 values below 0.70 were obtained after the simulation of assays using CC from in vitro assays that did not use the sinker, indicating that the computer program did not predict adhesion of the tablet to the bottom of the dissolution cell during the assay. The simulated dissolution profiles of the T1, T2 and T3 formulations were compared by f1 and f2 with the dissolution profiles of the market products. Such comparisons concluded that the software is not indicated as a substitute for in vitro assays when comparing dissolution profiles is desired

Hybrid magnetic scaffolds: The role of scaffolds charge on the cell proliferation and Ca2+ ions permeation.

Magnetic scaffolds with different charge densities were prepared using magnetic nanoparticles (MNP) and xanthan gum (XG), a negatively charged polysaccharide, or hydroxypropyl methylcellulose (HPMC), an uncharged cellulose ether. XG chains were crosslinked with citric acid (cit), a triprotic acid, whereas HPMC chains were crosslinked either with cit or with oxalic acid (oxa), a diprotic acid. The scaffolds XG-cit, HPMC-cit and HPMC-oxa were characterized by scanning electron microscopy (SEM), inductively coupled plasma atomic emission spectroscopy (ICP-AES), superconducting quantum interference device (SQUID) magnetometry, contact angle and zeta-potential measurements. In addition, the flux of Ca2+ ions through the scaffolds was monitored by using a potentiometric microsensor. The adhesion and proliferation of murine fibroblasts (NIH/3T3) on XG-cit, XG-cit-MNP, HPMC-cit, HPMC-cit-MNP, HPMC-oxa and HPMC-oxa-MNP were evaluated by MTT assay. The magnetic scaffolds presented low coercivity (<25Oe). The surface energy values determined for all scaffolds were similar, ranging from 43mJm-2 to 46mJm-2. However, the polar component decreased after MNP incorporation and the dispersive component of surface energy increased in average 1mJm-2 after MNP incorporation. The permeation of Ca2+ ions through XG-cit-MNP was significantly higher in comparison with that on XG-cit and HPMC-cit scaffolds, but through HPMC-cit-MNP, HPMC-oxa and HPMC-oxa-MNP scaffolds it was negligible within the timescale of the experiment. The adhesion and proliferation of fibroblasts on the scaffolds followed the trend: XG-cit-MNP>XG-cit>HPMC-cit, HPMC-cit-MNP, HPMC-oxa, HPMC-oxa-MNP. A model was proposed to explain the cell behavior stimulated by the scaffold charge, MNP and Ca2+ ions permeation.

Sustainable hydroxypropyl methylcellulose/xyloglucan/gentamicin films with antimicrobial properties.

Hydroxypropyl methylcellulose (HPMC) and xyloglucan (XG) crosslinked with citric acid over a range of HPMC/XG weight ratios formed sustainable blend films characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, tensile tests, circular dichroism and determination of inhibitory activity against Staphylococcus aureus and Escherichia coli. Both in solution and in the crosslinked films, HPMC chains lost the original ordered conformation upon interacting with XG, giving rise to an entropic gain. The highest values of tensile strength (25MPa) and Young's modulus (689MPa) occurred for the 50:50 HPMC/XG blend films. In vitro loading of gentamicin sulfate (GS) in the films amounted to 0.18±0.05 -0.37±0.05g of GS per g polymer. At pH 7.4 and 37°C, the GS release kinetics from the films fitted with the Korsmeyer-Peppas model revealed a non-Fickian release mechanism with diffusional coefficient n∼0.7. The cross-linked films of HPMC, XG and their blends loaded with GS showed outstanding antibacterial activity against Staphylococcus aureus and Escherichia coli, disclosing their potential for novel biomedical applications.

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.

Biopolymeric antimicrobial films: study of the influence of hydroxypropyl methylcellulose, tapioca starch and glycerol contents on physical properties.

Mixture design methodology was applied to study the effect of different levels of tapioca starch (TS), hydroxypropyl methylcelullose (HPMC), and glycerol (Gly) on the physical properties of biopolymeric films supporting potassium sorbate (KS; 0.3% w/w) with the goal of contributing to the development of materials for preventing food surface contamination. Mechanical properties, water vapour permeability (WVP), solubility in water (S) and colour attributes were evaluated on the films. HPMC addition produced an increase of elastic modulus (Ec), stress at break (σb) and S. It also decreased the yellow index (YI) values and the strain at break (εb). The study was deepened using the formulation containing 2.67 g/100g of TS, 0.67 g/100g of HPMC, 1.67 g/100g Gly and 0.3g/100g KS, observing that it behaved as an effective antimicrobial barrier against Zygosaccharomyces bailii external contamination. Microstructural analysis allowed us to conclude that HPMC incorporation to a TS network decreased roughness of the films and it also increased permeability to oxygen (PO2).

Enhancement of solubility and dissolution rate of poorly water soluble raloxifene using microwave induced fusion method

The objective of the present work was to enhance the solubility and dissolution rate of the drug raloxifene HCl (RLX), which is poorly soluble in water. The solubility of RLX was observed to increase with increasing concentration of hydroxypropyl methylcellulose (HPMC E5 LV). The optimized ratio for preparing a solid dispersion (SD) of RLX with HPMC E5 LV using the microwave-induced fusion method was 1:5 w/w. Microwave energy was used to prepare SDs. HPMC E5 LV was used as a hydrophilic carrier to enhance the solubility and dissolution rate of RLX. After microwave treatment, the drug and hydrophilic polymer are fused together, and the drug is converted from the crystalline form into an amorphous form. This was confirmed through scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies. These results suggested that the microwave method is a simple and efficient method of preparing SDs. The solubility and dissolution rate of the SDs were increased significantly compared with pure RLX due to the surfactant and wetting properties of HPMC E5 LV and the formation of molecular dispersions of the drug in HPMC E5 LV. It was concluded that the solubility and dissolution rate of RLX are increased significantly when an SD of the drug is prepared using the microwave-induced fusion method.

O objetivo do presente trabalho foi aumentar a solubilidade e taxa de dissolução do cloridrato de raloxifeno (RLX), que é pouco solúvel em água. A solubilidade do RLX aumentou com o aumento da concentração de hidroxipropilmetilcelulose (HPMC E5 LV). A proporção otimizada para a preparação de uma dispersão sólida (DS) de RLX com HPMC E5 LV utilizando o método de fusão induzida por microondas foi de 1:5 (p/p). A energia do microondas foi usada para preparar DS. O HPMC E5 LV foi utilizado como veículo hidrofílico para aumentar a solubilidade e a taxa de dissolução de RLX. Após o tratamento por microondas, o polímero hidrofílico e o fármaco são fundidos em conjunto, sendo o fármaco convertido da forma cristalina para a amorfa. Confirmou-se por meio de microscopia eletrônica de varredura (MEV), calorimetria exploratória diferencial (DSC) e difração de raios X do pó (PXRD). Estes resultados sugerem que o método de microondas é simples e eficiente para a preparação de DS. A solubilidade e taxa de dissolução de DS foram aumentadas, significativamente, em comparação com RLX puro devido às propriedades tensoativas e umectantes de HPMC E5 LV e à formação de dispersões moleculares do fármaco em HPMC E5 LV. Concluiu-se que a solubilidade e a taxa de dissolução de RLX foram significativamente aumentadas quando a DS do fármaco é preparada utilizando o método de fusão induzida por microondas.

Cefuroxime axetil loaded gastroretentive floating tabletsbased on hydrophilic polymers: preparation and in vitro evaluation

The aim of this work was to study the formulation and in vitro characterization of hydro dynamically balanced floating matrix tablets using Cefuroxime axetil (CA) as model drug. Different excipients such as hydroxy propyl methyl cellulose (HPMC) K15M, E5LV (gelling agent), sodium bicarbonate (gas generating agent) and sodium lauryl sulfate (SLS) (solubility enhancer) were used in order to optimize the drug release profile as well as floating property. Decrease in release characteristics with high viscous polymer were observed due to increased gel strength, tortuosity and length of drug diffusion path. Significant difference (p<0.5) in release rate was found at different concentration of SLS. The release mechanisms were explored and explained with zero order, first order, Higuchi, Korsmeyer and Hixson-Crowell equations. The release rate, extent and mechanism were governed by the content of polymer. The polymer content and amount of floating agent significantly affected the time required for 50%of drug release (t50%), mean dissolution time (MDT), release rate constant, and diffusion exponent (n).Kinetic modeling of dissolution profile revealed that the drug release mechanism could range from diffusion controlled to case II transport, which was co-dominated by diffusion polymer erosion in the release mechanism.

Programmed delivery of verapamil hydrochloride from tablet in a capsule device

The aim of the present work was to develop a programmed drug delivery system which would be able to release the drug after 6 h of lag time by use of hydrophilic polymers. The capsule body was made impermeable by use of formaldehyde vapor treatment, while the cap was untreated. The capsule was filled with two layered tablets (tablet-in-capsule), followed by a sodium bicarbonate:citric acid mixture (SBCM) and lactose as bulking agent. Sodium alginate, chitosan, HPMC K15 and chitosan:sodium alginate complex (CSAC) were used as the rate modulating layer. Through combined use of HPMC K15 and adjusting the ratio of CSAC, the desired lag time of 6 h was obtained. The effect of the bulking agents on the lag time were also studied and it was found that the lag time was decreased with higher amounts of lactose, and delayed dissolution and decreased lag time was observed at higher amount of effervescent mixture.

O objetivo do presente trabalho foi desenvolver sistema de liberação programada de cloridrato de verapamil capaz de liberação imediata do fármaco após 6 h de intervalo de tempo usando polímeros hidrofílicos. O corpo da cápsula foi impermeabilizado por tratamento de vapor de formaldeído, enquanto a tampa não foi submetida ao tratamento. Dois comprimidos foram inseridos na cápsula (comprimidos em cápsula) seguido de mistura de bicarbonato de sódio: ácido cítrico e lactose, utilizados como excipientes. O alginato de sódio, a quitosana, o HPMC K15 e o complexo quitosana:alginato de sódio foram utilizados para modular a razão de liberação do fármaco. A combinação entre o HPMC K15 e o ajuste da proporção do complexo quitosana:alginato de sódio permitiu a liberação do fármaco após 6 h. O efeito dos excipientes na liberação do fármaco foi também avaliado. Verificou-se que o tempo de latência foi reduzido na presença de maior quantidade de lactose, enquanto o menor tempo foi observado empregando maior concentração da mistura efervescente.