Autologous serum eye drops diluted with 0.5% methylcellulose and 0.9% saline solution: a clinical comparative study / Colírio de soro autólogo diluído com metilcelulose 0,5% e solução salina 0,9%: um estudo clínico comparativo

ABSTRACT Purpose: This clinical study compared autologous serum eye drops diluted with 0.5% methylcellulose and 0.9% saline solution. The subjective criteria for symptom improvement and the objective clinical criteria for response to therapy were evaluated. Methods: This longitudinal prospective study enrolled 23 patients (42 eyes) with persistent epithelial defects or severe dry eye disease refractory to conventional therapy who had been using autologous serum 20% prepared with methylcellulose for > 6 months and started on autologous serum diluted in 0.9% saline solution. The control and intervention groups consisted of the same patients under alternate treatments. The subjective criteria for symptom relief were evaluated using the Salisbury Eye Evaluation Questionnaire. The objective clinical criteria were evaluated through a slit-lamp examination of the ocular surface, tear breakup time, corneal fluorescein staining, Schirmer's test, rose Bengal test, and tear meniscus height. These criteria were evaluated before the diluent was changed and after 30, 90, and 180 days. Results: In total, 42 eyes were analyzed before and after 6 months using autologous serum diluted with 0.9% saline. No significant differences were found in the subjective criteria, tear breakup time, tear meniscus, corneal fluorescein staining, or rose Bengal test. Schirmer's test scores significantly worsened at 30 and 90 days (p=0.008). No complications or adverse effects were observed. Conclusions: This study reinforces the use of autologous serum 20% as a successful treatment for severe dry eye disease resistant to conventional therapy. Autologous serum in 0.9% saline was not inferior to the methylcellulose formulation and is much more cost-effective.

RESUMO Objetivo: Este estudo comparou o colírio de soro au tólogo manipulado com metilcelulose a 0,5% com solução salina 0,9%. Critérios subjetivos de melhora dos sintomas e critérios clínicos objetivos para resposta à terapia foram avaliados. Métodos: Este estudo prospectivo longitudinal envolveu 23 pacientes (42 olhos) com defeitos epiteliais persistentes ou doença de olho seco grave refratária à terapia convencional que usavam colírio de soro autólogo 20% preparado com metilcelulose por mais de 6 meses e iniciaram soro autólogo diluído em solução salina 0,9%. Os grupos controle e intervenção consistiam dos mesmos pacientes sob tratamentos alternados. Os critérios subjetivos para o alívio dos sintomas foram avaliados usando o Salisbury Eye Evaluation Questionnaire. Os critérios objetivos foram avaliados por meio de exame em lâmpada de fenda incluindo: tempo de ruptura da lágrima, coloração da córnea com fluoresceína, teste de Schirmer, coloração com rosa bengala e altura do menisco lacrimal. Esses critérios foram avaliados antes da troca do diluente e após 30, 90 e 180 dias. Resultados: Um total de 42 olhos foram analisados antes e após 6 meses usando soro autólogo diluído com solução salina 0,9%. Nenhuma diferença significativa foi encontrada nos critérios subjetivos, tempo de ruptura da lágrima, menisco lacrimal, coloração com fluoresceína ou rosa bengala. Os resultados dos testes de Schirmer pioraram significativamente em 30 e 90 dias (p=0,008). Não foram observadas complicações ou efeitos adversos. Conclusões: Este estudo reforça o uso do colírio de soro autólogo 20% como um tratamento de sucesso para a doença do olho seco grave resistente à terapia convencional. O soro autólogo diluído em solução salina a 0,9% não foi inferior à formulação de metilcelulose.

Preparation and evaluation of sirolimus sustained release tablets based on mesoporous silicon loaded self-microemulsion / 药学学报

Sirolimus self-microemulsion-mesoporous silicon sustained release tablets were prepared in order to improve the dissolution of the insoluble drug sirolimus and reduce its side effects. Firstly, sirolimus self-microemulsion was prepared and cured with mesoporous silicon. Secondly, the suitable excipients were selected according to the appearance, hardness and in vitro release rate. The sustained-release tablets with hydroxypropyl methylcellulose (HPMC) as skeleton material were prepared by powder direct pressing method, and the formulation was optimized by central composite design-response surface method to investigate the drug release in vitro. Finally, the pharmacokinetics was carried out in beagle dogs using the commercial sirolimus tablets as references. The final formulation of sustained-release tablets is as follows: 162 mg of sirolimus self-microemulsion-mesoporous silica (1∶1, w/w), 80 mg of HPMC K4M and 80 mg of carboxymethyl starch sodium, the microcrystalline cellulose is 168 mg. The results of in vitro release test showed that the self-made sustained-release tablets released slowly within 12 h, which conformed to the Ritger-Peppas model. The in vivo test results showed that compared with the commercial sirolimus tablets, the Cmax of the sustained-release tablets decreased by 49.47%, the Tmax of the sustained-release tablets was prolonged by 5.1 times, and the relative bioavailability was 105.81%. Sirolimus self-microemulsion-mesoporous silicon sustained-release tablets have good sustained-release effects in vitro and in vivo, which provides a reference for the solubilization of other insoluble drugs and the research and development of sustained-release preparations. Animal experiments and welfare processes were reviewed and approved by the Animal Ethics Committee of the 900TH Hospital of the Joint Logistics support Force.

Characterization of the critical quality attributes for hydroxypropyl methylcellulose with different sources and analysis of the release of sustained-release tablets in vitro / 药学学报

The quality difference of pharmaceutical excipients from different sources affects the molding properties of the powder, resulting in changes in the properties of the final product. In this study, the critical quality attributes of hydroxypropyl methylcellulose (HPMC) with different specifications from two manufacturers (manufacturer A and manufacturer B) were characterized including particle size, physical morphology, viscosity and powder physical quality attributes. Aminophylline, diclofenac sodium, and metformin hydrochloride were utilized as model drugs with different solubility to prepare sustained-release tablets, and the effect of HPMC from different sources on drug release of sustained-release tablets in vitro was investigated. The results showed that HPMC with the same viscosity specification from different sources had outstanding differences in the physicochemical properties (including particle size, physical morphology, viscosity, dimension, compressibility and powder flow), which could change the hardness and friability of the sustained-release tablets. The differences in the physicochemical properties of HPMC had different effects on the dissolution of different sustained-release tablets in vitro. It had no significant effect on the release of easily soluble aminophylline and metformin hydrochloride, but had a greater impact on the release of poorly soluble diclofenac sodium. Compared with manufacturer A, the sustained-release effect of matrix tablets prepared by HPMC from manufacturer B was more excellent. The results of this study will provide a theoretical reference on selecting the appropriate excipients for formulation design.

Study on injectable calcium sulfate bone cement rich in bioactivity / 中华骨科杂志

Objective:To explore the effect of decalcified bone matrix (DBM) rich in biological activity on surgical-grade medical calcium sulfate, and to observe the change of different content of DBM on the physical and chemical properties of calcium sulfate, which provide theoretical basis for the preparation of calcium sulfate bone cement with osteogenic and injectable properties.Methods:DBM with weight content of 0, 5%, 10%, 20%, 30%, 40% was fully mixed with CSH. Dissolve 0.3 g of methyl cellulose in 10 ml of deionized water to prepare a 3% methyl cellulose solution. Methylcellulose solution was added according to the liquid-solid ratio of 0.4. The mixture was evenly stirred to form slurry, then the degradation rate, compressive strength, setting time and and pH value of calcium sulfate in vitrowas measured.Results:The initial setting time and final setting time of calcium sulfate were 4.96±0.20 and 5.83±0.12 min respectively. With the increase of DBM content, the initial setting time and final setting time increased significantly ( F=49.275, P<0.05; F=124.859, P<0.05). The compressive strength of pure calcium sulfate is 23.33±6.35 MPa; when the content is 40%, the compressive strength is only 3.33 MPa. With the increase of DBM content, the compressive strength first increased and then decreased; the content of 5%, 10%, 20% DBM had little effect on the compressive strength ( P>0.05), while the compressive strength of 30% and 40% groups decreased significantly ( t=3.259, P<0.05). DBM with different contents can significantly change the degradation rate of calcium sulfate complex. When the content of DBM is 30% and 40%, the complete degradation time in vivo is only 10 d, while the degradation rate of calcium sulfate is 63% in 30 d. At any time point in vitro degradation, DBM had no significant effect on the pH value of calcium sulfate complex culture medium, and the change law was consistent with that of pure calcium sulfate. Conclusion:With the increase of DBM content, the degradation rate is gradually accelerated, the compressive strength is reduced, and the setting time is prolonged, which is not conducive to the preparation of injectable calcium sulfate cement.

Characterization and principal component analysis of functionality-related characteristics of hydroxypropyl methylcellulose type 2208 / 药学学报

Under the guidance of Chinese Pharmacopoeia (2020 edition), the functionality-related characteristics of hydroxypropyl methylcellulose (HPMC) type 2208 from imported A manufacturer, domestic S manufacturer, domestic T manufacturer and different batches of the same manufacturer were characterized. The principal component analysis was used to comprehensively evaluate the functionality-related characteristics. The results were as follows: hydroxypropyl methylcellulose had no significant difference in viscosity and molecular weight distribution between different manufacturers, and there were significant differences in the cumulative particle size distribution of the sample reaches 50% (d50) and 90% (d90), bulk density, tap density and Carr's index. The HPMC from A manufacturer have the biggest inter-batch difference of particle size and their inter-batch difference of polydispersion coefficientis smaller than S manufacturer. Domestic manufactures have the largest inter-batch difference in other functionality-related characteristics. The three principal components were extracted by principal component analysis, and the variance contribution rate reached 89.44%, indicating that the extracted principal components can explain all the data well. By constructing a comprehensive evaluation model, the comprehensive score ranking of all HPMC samples is obtained: S manufacturer > A manufacturer > T manufacturer.

Preparation And Characterization Of Hydroxypropyl Methylcellulose Produced From Α-Cellulose Betung Bamboo (DENDROCALAMUS Asper) And It’s Evaluation On Gel Formulation

Objective: This study aim to obtain the optimum condition of preparation of hydroxypropyl methylcellulose (HPMC) produced from α-cellulose betung bamboo, physicochemical properties of HPMC powder and its characteristics in a gel formulation. Methods: HPMC of betung bamboo (HPMC BB) were optimized by central composite design (CCD) using three variables (sodium hydroxide concentration, dimethyl sulfate concentration, and temperature) and five levels (0,±1, and±α). The suggested optimum condition was subjected to further characterization. HPMC BB was characterized using Fourier transform infrared (FTIR) spectrometry, particle size analyzer (PSA), x-ray diffraction (XRD), scanning electron microscope (SEM) and compared to HPMC 60SH as the reference. Then, HPMC BB was used as a gelling agent in a gel formulation and the gel was evaluated, including appearance and homogeneity, pH, viscosity, and spreadability. Results: Optimum condition of preparation of HPMC BB was using sodium hydroxide 27.68% (w/v) and 1.26 ml dimethyl sulfate (based on 1 g α-cellulose) at 58.11 °C which resulted in molar substitution 0.21 and degree of substitution 2.09. The results showed that HPMC BB was a fine powder with yellowish-white color, odorless and tasteless, pH 7.02, residue on ignition 1.39%, methoxy groups content 28.56%, hydroxypropoxy groups content 7.09%, mean particle size 98.595 μm, loss on drying 3.62%, and moisture content 7.47%. Flow properties of HPMC BB classified in the fair category. The infrared spectrum and diffraction patterns were relatively similar to HPMC 60SH. The gel has a good homogeneity and spreadability and viscosity 142.5 mPa⋅s. pH 6.37. Conclusion: Based on the comparison to reference, HPMC BB showed relatively similar physicochemical and powder properties. However, HPMC BB is not recommended as a gelling agent in gel formulation because it has a low viscosity.

Neurotrophin-3 modified hyaluronan-methylcellulose hydrogel promotes neurological function in rats with spinal cord injury / 中国组织工程研究

BACKGROUND: Hyaluronan-methylcellulose hydrogel cannot only be conjugated with short peptide sequences and growth factors to achieve sustained release, but also has a role in blocking dural defects and reducing inflammation. It is an ideal biomaterial for the treatment of spinal cord injury. OBJECTIVE: To investigate the effect of neurotrophin-3 modified hyaluronan-methylcellulose (HAMC-NT-3) hydrogel on the recovery of neurological function in rats with spinal cord injury. METHODS: Fifty-four female Sprague-Dawley rats (provided by the Experimental Animal Center of the Academy of Military Medical Sciences in China) were randomly divided into three groups (n=18 per group) . The sham group only underwent T10 laminectomy. In the model group and the experimental group, an aneurysm clip was used to establish spinal cord injury models after T10 laminectomy. The experimental group was locally injected with HAMC-NT-3 hydrogel. The Basso Beattie Bresnahan function scoring was performed at 1 day, 1, 2, 3, 4, 5, 6, 7, and 8 weeks after surgery. The inclined plane test was performed at 4, 6 and 8 weeks after surgery to evaluate the recovery of hindlimb motor function. ELISA was used to detect the concentrations of inflammatory factors in the spinal cord at 1 week after surgery. Immunohistochemical staining was used to observe the area of syringomyelia, glial fibrillary acidic protein expression and nerve regeneration at 8 weeks after surgery. RESULTS AND CONCLUSION: (1) The Basso Beattie Bresnahan scores of the model group and the experimental group were lower than those of the sham group at various time points after surgery (P < 0.05) . The Basso Beattie Bresnahan scores of the experimental group were higher than those of the model group at 4-8 weeks after surgery (P < 0.05) . (2) In the inclined plane test, the maximum inclined angles of the model group and the experimental group at each time point after surgery were lower than that of the sham group (P < 0.05) . The maximum inclined angles of the experimental group at 6 and 8 weeks after surgery were higher than those of the sham group (P < 0.05) . (3) The concentrations of tumor necrosis factor-α, interleukin-1β, interleukin-6 and interleukin-10 in the experimental group and the model group were higher than those in the sham group (P < 0.05) . The concentrations of tumor necrosis factor-α, interleukin-1β and interleukin-6 in the experimental group were lower than those in the model group (P < 0.05) . The concentration of interleukin-10 in the experimental group was higher than that in the model group (P < 0.05) . (4) Immunohistochemical staining showed that the expression levels of glial fibrillary acidic protein in the experimental group and the model group were higher than those in the sham group, while the expression of glial fibrillary acidic protein in the experimental group was lower than that in the model group. The area of syringomyelia in the experimental group was smaller than that in the model group (P < 0.05) . These results indicate that local injection of HAMC-NT-3 hydrogel can effectively inhibit inflammation as well as astrocyte activation and proliferation, reduce fibrous scar formation, and promote the protection of nerve tissue and the recovery of hindlimb motor function after spinal cord injury.

Physical properties and biological effects of mineral trioxide aggregate mixed with methylcellulose and calcium chloride

Abstract Objectives: Methylcellulose (MC) is a chemical compound derived from cellulose. MTA mixed with MC reduces setting time and increases plasticity. This study assessed the influence of MC as an anti-washout ingredient and CaCl2 as a setting time accelerator on the physical and biological properties of MTA. Material and Methods: Test materials were divided into 3 groups; Group 1(control): distilled water; Group 2: 1% MC/CaCl2; Group 3: 2% MC/CaCl2. Compressive strength, pH, flowability and cell viability were tested. The gene expression of bone sialoprotein (BSP) was detected by RT-PCR and real­ time PCR. The expression of alkaline phosphatase (ALP) and mineralization behavior were evaluated using an ALP staining and an alizarin red staining. Results: Compressive strength, pH, and cell viability of MTA mixed with MC/CaCl2 were not significantly different compared to the control group. The flowability of MTA with MC/CaCI2 has decreased significantly when compared to the control (p<.05). The mRNA level of BSP has increased significantly in MTA with MC/CaCl2 compared to the control (p<.05). This study revealed higher expression of ALP and mineralization in cells exposed to MTA mixed with water and MTA mixed with MC/CaCl2 compared to the control (p<.05). Conclusions: MC decreased the flowability of MTA and did not interrupt the physical and biological effect of MTA. It suggests that these cements may be useful as a root-end filling material.

Floating ability and drug release evaluation of gastroretentive microparticles system containing metronidazole obtained by spray drying

Abstract Gastroretentive floating microparticles were developed and evaluated for the controlled metronidazole delivery for treatment of gastric disease. Floating microparticles, varying in proportions of chitosan and hydroxypropyl methylcellulose or ethylcellulose, were obtained by spray drying. Floating microparticles were characterized by physicochemical and in vitro studies, according to their floating ability and drug delivery. Microparticles presented mean diameter from 1.05 to 2.20 µm. The infrared spectroscopy confirmed the drug encapsulation and showed no chemical linkage between microparticles components. X-ray diffraction showed changes in the drug`s solid state, from crystalline to amorphous, indicating partial drug encapsulation, due to the presence of some crystalline peaks of metronidazole in microparticles. All microparticles floated immediately in contact of simulated gastric fluid and both floating and drug release profiles were dependent of microparticles composition. Microparticles samples constituted by chitosan and hydroxypropyl methylcellulose revealed the best relationship between floating duration and drug release, remaining floating during the occurrence of the drug release, ideal condition for the floating gastroretentive systems.

In vitro evaluation of sustained released matrix tablets containing ibuprofen: a model poorly water-soluble drug

ABSTRACT A matrix system was developed that releases ibuprofen (IB) over a 12-hour period and the influence of the polymer type and concentration on the release rate of the drug was evaluated. Tablets containing different concentrations of Carbopol (CP), hydroxypropyl methylcellulose (HPMC), or ethyl cellulose (EC) were prepared using direct compression and the drug content, content uniformity, hardness, friability, dissolution performance, and in vitro release kinetics were examined. Formulated tablets were found to be within acceptable limits for physical and chemical parameters. The release kinetics of the Carbopol(r)971P 8% formulation showed the best linearity (r 2 =0.977) in fitting zero-order kinetics, suggesting the release rate was time independent. The drug release from tablets containing 8% CP was extended over approximately 18 hours and the release kinetics were nearly linear, suggesting that this system has the potential to maintain constant plasma drug concentrations over 12 hours, which could reduce the frequency of administration and the occurrence of adverse effects associated with repeated administration of conventional IB tablets.

Aplicación y efecto de un recubrimiento comestible sobre la vida útil de la mora de castilla (Rubus glaucus Benth) / Edible coating application and effect on blackberry (Rubus glaucus Benth) shelf life

Antecedentes: En los últimos años ha incrementado el interés por el consumo de frutas en estado fresco debido al potencial nutricional que estas contienen. Además, por el alto consumo energético que se generan en la aplicación de una cadena en frío, se ha incursionado en la aplicación de recubrimientos comestibles como una técnica alternativa para la conservación de frutas. Objetivos: Por tal razón, este trabajo tuvo como objetivo aplicar un recubrimiento a base de hidroxipropil metilcelulosa con la inclusión de cera de abejas en mora de castilla y evaluar su efecto en la conservación de esta fruta. Métodos: Se trabajó con un diseño multifactorial categórico y el análisis estadístico utilizado fue el LSD de Fisher con un nivel de confianza del 95%; determinándose propiedades fisiológicas tales como respiración y pérdida de peso, propiedades fisicoquímicas como pH, acidez titulable, sólidos solubles totales e índice de maduración durante un periodo de 15 días a una temperatura de 4°C. Resultados: Se obtuvo diferencias significativas (p < 0,05) entre los tratamientos evaluados a partir del tercer día de almacenamiento tanto para los parámetros fisicoquímicos como fisiológicos. La acidez titulable tuvo un decrecimiento marcado en el tratamiento control (T5) con respecto a los tratamientos donde se aplicó los recubrimientos (T1, T2, T3, T4) donde el descenso de la acidez fue menor. Por otro lado, la pérdida de peso, los sólidos solubles totales, el pH, el índice de maduración y el índice de respiración incrementaron a medida que el tiempo de almacenamiento transcurrió, indicando que las moras tratadas con los recubrimientos tuvieron un incremento menor con respecto a las moras sin recubrimiento. Conclusiones: Los recubrimientos comestibles aplicados a la mora de castilla tuvieron un efecto positivo sobre las propiedades evaluadas, siendo los mejores tratamientos el T3 y T4. En general, la aplicación de un recubrimiento comestible a base de hidroxipropil metilcelulosa y cera de abejas logró aumentar la vida útil de la mora de castilla.

Background: On the last years the interest on fresh fruits consumption has been increased due to its nutritional potential as well as high energetic demand generated by the cold-chains storage. It is the reason why it has been dabbled on edible coating as an alternative method on fruits preservation. Objectives: This investigation focused on the coating application using a hydroxypropyl methylcellulose based with bees wax applied all over blackberry fruits in order to evaluate the effects on its preservation. Methods: A multifactorial categorical design was used through the Fisher LSD method as an statistical analysis with a confidence level of 95%; it were determined physiological properties such respiration and weight loss, and physicochemical properties like pH, titratable acidity, soluble solids, and ripeness index within a period of 15 days at 4°C. Results: It were obtained significant differences (p<0.05) between the evaluated treatments from the third storage day for physicochemical and physiological parameters. The titratable acidity has a marked decrease on the control treatment (T5) regarding treatments where coatings were applied (T1, T2, T3, T4) where a smaller decrease on acidity was obtained. In other hand, the weight loss, total soluble solids, pH, ripening and respiration index showed an increase over storage time. The blackberry fruits processed with edible coating presented a slight increase compared to control samples. Conclusions: Edible coatings applied on blackberry fruits had a positive effect in the evaluated properties, treatments T3 and T4. Generally, edible coatings with hydroxypropyl methylcellulose base and beeswax increase the shelf life of blackberry.

The swelling behavior of choline fenofibrate hydrogel matrix tablets using dynamic image analysis / 药学学报

The purpose of this study is to investigate the effects of formulation on the swelling behavior of choline fenofibrate hydrogel matrix tablets and reveal the relation between swelling property and release profile using dynamic image analysis. The volume swelling ratio (SR) and height/width (k) could evaluate the swelling behavior of matrix tablets well. The mount of hydroxypropyl methylcellulose (HPMC) and the ratio between K15M and K4M affected the volume swelling ratio, while PVP didn't. The three factors all impacted k, which was an indicator of the strength of the gel formed by HPMC. The accumulative release ratio and SR, the rate of swelling and the rate of release were compared. The proper model equations were established for the results with an excellent correlation. The results prove that there is a strong relevance between the swelling behavior and release property. This study provides a guideline in the study design for hydrogel matrix tablets.

Preparation and Release Characteristics of Venlafaxine Hydrochloride Hydrophilic and Lipidic Matrix Sus-tained-release Tablets / 中国药房

OBJECTIVE:To prepare Venlafaxine hydrochloride sustained-release tablets,and to investigate the characteristics of drug release. METHODS:Using glyceryl behenate as lipidic matrix material and HPMC as hydrophilic matrix material,the kind and dosage of excipients were screened by single factor experiment. Using 4,8,24 h accumulative release rate and the deviation summation of ideal values as index,the viscosity of HPMC,the amounts of HPMC K15M and glyceryl behenate were optimized by orthogonal test. The dissolution curves were fitted by different equations. RESULTS:The optimal formulation was as follows as venlafaxine hydrochloride 8.5 kg,HPMC K15M 15 kg,glyceryl behenate 26 kg,magnesium stearate 0.5 kg. 4,8,24 h accumula-tive release rates of prepared matrix sustained-release tablets were 34.3%,63.9% and 99.2%,respectively. The releases profiles of hydrophilic and lipidic matrix sustained release tablets followed first-order equation in vitro mainly through matrix erosion. CON-CLUSIONS:Venlafaxine hydrochloride hydrophilic and lipidic matrix sustained-release tablets with good sustained-release effect have been prepared successfully.

Effects of Hydrophilic Polymers on the Stability of Self-microemulsifying Drug Delivery Systems / 中国药房

OBJECTIVE:To investigate the effects of hydrophilic polymers on the stability of self-microemulsifying drug deliv-ery systems (SMEDDS). METHODS:Taking felodipine (FDP) as model drug,the content of FDP was determined by HPLC method. The effects of pure water,0.5% Kollidon VA64,HPMC E5,HPMC K100LV,HPMC K4M,PVP K30 solution,while 0.1%,0.5% and 1.0% HPMC E5 and Kollidon VA64 on residual content of dissolved FDP were determined in SMEDDS. RE-SULTS:The residual contents of dissolved FDP in SMEDDS placed in Kollidon VA64,HPMC E5,HPMC K100LV,PVP K30, HPMC K4M and pure water for 1 h were 92.7%,63.6%,50.2%,46.2%,36.0%and 24.0%,respectively. The order of maintain-ing the supersaturation state was Kollidon VA64>HPMC E5>HPMC K100LV>PVP K30>HPMC K4M>pure water. The residu-al contents of dissolved FDP in SMEDDS placed in 0.1%,0.5%,1% Kollidon VA64 and HPMC E5 and pure water for 1 h were 93.2%,95.1%,96.0% and 48.4%,62.1%,75.1%. CONCLUSIONS:Kollidon VA64 and HPMC E5 can significantly inhibit drug release in SMEDDS and be used as stabilizer of SMEDDS,wherein Kollidon VA64 was better.

Formulation and Characterization of Ketoprofen Emulgels.

The present study was intended to formulate the ketoprofen emulgels using different viscosity grades of hydroxypropyl methylcellulose and carbopol as gelling agents. All the prepared emulgels were shown acceptable physical properties concerning colour, homogeneity, consistency, and pH value. Emulgels containing hydroxypropyl methylcellulose were poor in clarity when compared to carbopol formulations. The influence of the type of gelling agent on the drug release from the prepared emulgels was investigated and carbopol 934 showed good results not only in the drug release but also in physical evaluation parameters. From the drug release studies, F3 formulation showed 98.46±2.05% drug release in 8 h with good clarity and physical appearance. The T10% and T80% values of best formulation F3 was found to be 0.9 h and 6.6 h respectively. The T10% and T80% was higher for formulations with carbopol in low concentration when compared to hydroxypropyl methylcellulose K 4M and K 15M in high concentrations, indicating better controlled release. FTIR studies proved the compatibility between drug and carbopol. From the stability studies, similarity index value between dissolution profiles of F3 formulation before and after storage was found to be 87.16. Hence the development of ketoprofen emulgels is a suitable way for topical administration.

Safety and feasibility of the use of a bevacizumab-methylcellulose mixture as an adjunct to glaucoma surgery: a pilot study / Segurança e viabilidade do uso de uma mistura de bevacizumabe-metilcelulose como terapia adjuvante à cirurgia anti-glaucomatosa: um estudo piloto

ABSTRACT Bevacizumab, a monoclonal anti-vascular endothelial growth factor antibody, has been suggested as a potential healing therapeutic following glaucoma surgery. Here, we aimed to improve the bioavailability of bevacizumab when used as an adjunct therapy to non-penetrating deep sclerectomy (DS) by using a bevacizumab-methylcellulose mixture (BMM). Ten previously non-operated eyes in ten patients diagnosed with primary open angle glaucoma underwent DS with a subconjunctival injection of 0.3 ml of BMM (bevacizumab 3.75 mg incorporated into 4% methylcellulose) at the surgical site. Bevacizumab release was evaluated in vitro using size-exclusion high performance liquid chromatography (HPLC). Intraocular pressure (IOP), bleb morphology, corneal endothelial cell count (CECC), and complications were evaluated at 6 months after surgery. Using HPLC, bevacizumab was detected in BMM for up to 72 h. Moreover, all surgical blebs remained expanded with hyaline material during the first week. A significant IOP reduction (mean ± SD= -10.3 ± 5.4 mmHg, P<0.001) and diffuse blebs were observed at the final follow-up period. Although CECC was slightly reduced (-7.4%), no complications were observed. In conclusion, bevacizumab was released from BMM, and the use of this innovative mixture yielded good results following DS with no complications. Further studies are required to determine its efficacy prior to establishing BMM as an adjunct treatment for penetrating and non-penetrating glaucoma surgeries.

RESUMO O bevacizumabe (um agente anti-fator de crescimento endotelial vascular) tem sido sugerido como potencial modulador cicatricial na cirurgia do glaucoma. Este estudo objetivou melhorar a biodisponibilidade do bevacizumabe, investigando a viabilidade de uma nova mistura de bevacizumabe-metilcelulose (BMM) como terapia adjuvante para a esclerectomia profunda não-penetrante (DS). Dez olhos sem cirurgias prévias de 10 pacientes com glaucoma primário de ângulo aberto foram submetidos à DS associada à uma injeção subconjuntival de 0,3 ml da mistura de bevacizumabe-metilcelulose (bevacizumabe 3,75 mg incorporado em metilcelulose 4%) no sítio cirúrgico. A liberação de bevacizumabe foi avaliada in vitro através de cromatografia líquida de alta performance por exclusão de tamanho (HPLC). A pressão intraocular (PIO), a morfologia da ampola de filtração, a contagem de células endoteliais da córnea (CECC) e as complicações foram estudadas aos seis meses de seguimento. O bevacizumabe foi detectado a partir da mistura de bevacizumabe-metilcelulose por meio do HPLC até 72 horas. Além disso, todas as ampolas cirúrgicas permaneceram expandidas com material hialino durante a primeira semana. Uma redução significativa da pressão intraocular (média ± DP= -10,3 ± 5,4 mmHg, P<0,001) e ampolas difusas foram observadas ao final do período de seguimento. Embora a contagem de células endoteliais da córnea se mostrou discretamente diminuída (-7,4%), nenhuma complicação foi observada. Neste estudo, o bevacizumabe foi liberado da mistura de bevacizumabe-metilcelulose e o uso desta nova mistura se associou com bons resultados cirúrgicos e nenhuma complicação. Estudos futuros serão necessários para determinar sua eficácia, antes de se estabelecer a mistura de bevacizumabe-metilcelulose como um tratamento adjuvante às cirurgias penetrantes e não-penetrantes para o glaucoma.

Cloning, expression and characterization of the endoglucanase gene from Bacillus subtilis UMC7 isolated from the gut of the indigenous termite Macrotermes malaccensis in Escherichia coli

Background Bacillus subtilis UMC7 isolated from the gut of termite Macrotermes malaccensis has the ability to secrete a significant amount of extracellular endoglucanase, with an enzyme activity of 0.12 ± 0.01 μmol/min/mL. However, for economically viable industrial applications, the enzyme needs to be expressed in a heterologous host to overcome the low enzyme production from the wild-type strain. Results The endoglucanase gene from B. subtilis UMC7 was successfully cloned and expressed. A higher enzyme activity was observed in the intracellular fraction of the recombinant clone (0.51 ± 0.02 μmol/min/mL) compared with the cell-bound fraction (0.37 ± 0.02 μmol/min/mL) and the extracellular fraction (0.33 ± 0.01 μmol/min/mL). The recombinant endoglucanase was approximately 56 kDa, with optimal enzyme activity at 60°C and pH 6.0. The activity of the enzyme was enhanced by the addition of Ca2 +. However, the enzyme was inhibited by other metal ions in the following order: Fe3 + > Ni2 + > Cu2 + > Mn2 + = Zn2 + > Mg2 + > Cd2 + > Cr2 +. The enzyme was able to hydrolyze both low- and high-viscosity carboxymethyl-cellulose (CMC), avicel, cotton linter, filter paper and avicel but not starch, xylan, chitin, pectin and p-nitrophenyl α-d-glucopyranoside. Conclusions The recombinant endoglucanase showed a threefold increase in extracellular enzyme activity compared with the wild-type strain. This result revealed the potential of endoglucanase expression in E. coli, which can be induced for the overexpression of the enzyme. The enzyme has a broad range of activity with high specificity toward cellulose.

Microbial monitoring analysis of methylcellulose eye drops during use and storage / 中华实验眼科杂志

Background It is imperative for the microbial monitor after opening the bottle of eyedrops in order to ensure the safety during use of ophthalmic solutions with multi-dose packaging.Objective This study was to research the microbiological properties and sterile duration of methylcellulose (MC) eye drops in three common environmental conditions,including room temperature condition of community,refrigeration condition of community and room temperature condition of hospital.Methods MC eye drops were assigned to the community room temperature group,community refrigeration group and hospital room temperature group,and 200 bottles of MC eye drops with or without ethylparaben were collected in each group,including sealed or unsealed drugs at average.The containers of all the eye drops were opened and the opening times were record.The drugs was admistered 1 drop for 3 times per day,with the opening period for 5-10 seconds.Then the drugs were preserved in different environments based on grouping.Microbial isolation and purification were performed by the same lab technician at 8:00 from 1 through 10 days after opening of drugs with automatic microbial analyzer.Results In the unsealed MC eye drops without ethylparaben,the bacterial positive rates were about 30％ in the community room temperature group,community refrigeration group and hospital room temperature group,but no microbial colony was seen in the sealed eye drops.Ten days after opening of containers,the bacterial cultured rates were 30％,32％ and 36％ in the eye drops without ethylparaben in the community room temperature group,community refrigeration group and hospital room temperature group,and those in the eye drops with ethylparaben were 15％,19％ and 23％,respectively,showing significant differences between the eye drops with and without ethylparaben (x2 =6.452,4.448,4.063,all at P＜0.05).The 95％ confidence interval (CI) of difference values of intergroup bacterial rates were-0.166-0.126,-0.110-0.190 and-0.088-0.208 between the community room temperature group and the community refrigeration group,between the hospital room temperature group and the community refrigeration group,between the hospital room temperature group and the community room temperature group respectively in the unsealed eye drops without ethylparaben,and those in the unsealed eye drops with ethylparaben were-0.159-0.079,-0.089-0.169 and-0.043-0.203 respectively,indicating insignificant differences among the groups.Cultured bacteria were identified as Micrococcus luteus,Acinetobacter lwoffii,Bacillus subtilis,Acinetobacter radioresistens,Myroides and Staptococcus xylosus.Conclusions Ethylparaben can reduce the contamination rate of microorganisms after opening of MC eye drops.Three environmental conditions do not play an influence on microbial contamination of MC eye drops after opening.The bacteria of contaminated eye drops appear to be common microorganisms in atmosphere and soil,rather than eye common pathogens.

Preparation and characterization of ginsenoside Rg3 solid dispersion / 中国药学杂志

OBJECTIVE: To prepare ginsenoside Rg3 (G-Rg3) solid dispersion by atoping a new technology to increase the solubility of G-Rg3. METHODS: Hydroxypropyl methylcellulose acetate succinate (HPMCAS) was selected as the carrier to prepare G-Rg3 solid dispersion. The G-Rg3 solid dispersion was characterized via Fourier transform infrared spectroscopy, X-ray diffractometry, differential scanning calorimetry analysis, and scanning electron microscopy. The equilibrium solubility of G-Rg3 and G-Rg3 solid dispersion were measured by using high-performance liquid chromatography. RESULTS: The G-Rg3 solid dispersion was successfully prepared. The solubility of G-Rg3 solid dispersion in the weak acid medium (pH 5.5 and 6.4) designed to simulate human duodenum and jejunum was significantly higher than that of G-Rg3. CONCLUSION: The preparation method of G-Rg3 solid dispersion is simple, economic, and practical, which can obviously increase the of solubility of G-Rg3.

Use of hydrophilic and hydrophobic polymers for the development of controlled release tizanidine matrix tablets

The aim of the present study was to develop tizanidine controlled release matrix. Formulations were designed using central composite method with the help of design expert version 7.0 software. Avicel pH 101 in the range of 14-50% was used as a filler, while HPMC K4M and K100M in the range of 25-55%, Ethylcellulose 10 ST and 10FP in the range of 15 - 45% and Kollidon SR in the range of 25-60% were used as controlled release agents in designing different formulations. Various physical parameters including powder flow for blends and weight variation, thickness, hardness, friability, disintegration time and in-vitro release were tested for tablets. Assay of tablets were also performed as specified in USP 35 NF 32. Physical parameters of both powder blend and compressed tablets such as compressibility index, angle of repose, weight variation, thickness, hardness, friability, disintegration time and assay were evaluated and found to be satisfactory for formulations K4M2, K4M3, K4M9, K100M2, K100M3, K100M9, E10FP2, E10FP9, KSR2, KSR3 & KSR9. In vitro dissolution study was conducted in 900 ml of 0.1N HCl, phosphate buffer pH 4.5 and 6.8 medium using USP Apparatus II. In vitro release profiles indicated that formulations prepared with Ethocel 10 standard were unable to control the release of drug while formulations K4M2, K100M9, E10FP2 & KSR2 having polymer content ranging from 40-55% showed a controlled drug release pattern in the above mentioned medium. Zero-order drug release kinetics was observed for formulations K4M2, K100M9, E10FP2 & KSR2. Similarity test (f 2) results for K4M2, E10FP2 & KSR2 were found to be comparable with reference formulation K100M9. Response Surface plots were also prepared for evaluating the effect of independent variable on the responses. Stability study was performed as per ICH guidelines and the calculated shelf life was 24-30 months for formulation K4M2, K100M9 and E10FP2.

O objetivo do presente estudo foi desenvolver matriz de de tizanidina de liberação controlada. As formulações foram projetadas usando o método do componente, central com a ajuda de software Design expert(r), versão 7.0. Utilizou-se Avicel pH 101, no intervalo de 14-50%, como material de preenchimento, enquanto HPMC K4M e K100M, no intervalo de 25-55%, Etilcelulose 10 ST e 10FP, no intervalo de 15-45% e Kollidon SR, na faixa de 25-60% foram utilizados como agentes de liberação controlada, no planejamento de formulações diferentes. Vários parâmetros físicos, incluindo o fluxo de pó para as misturas e variação de peso, espessura, dureza, friabilidade, tempo de desintegração e liberação in vitro, foram testados para comprimidos. Ensaios dos comprimidos foram, também, realizados, tal como especificado em USP 35 NF 32. Avaliaram-se os parâmetros físicos de ambos, mistura em pó e comprimidos, como índice de compressibilidade, ângulo de repouso, variação de peso, espessura, dureza, friabilidade, tempo de desintegração e de ensaio, considerando-os satisfatórios para as formulações K4M2, K4M3, K4M9, K100M2, K100M3, K100M9, E10FP2, E10FP9, KSR2, KSR3 e KSR9. O estudo de dissolução in vitro foi realizado em 900 mL de HCl 0,1 N, tampão de fosfato pH 4,5 e meio 6,8, usando aparelho USP II. Os perfis de liberação in vitro indicaram que as formulações preparadas com Ethocel 10 padrão não foram capazes de controlar a liberação do fármaco, enquanto as formulações K4M2, K100M9, E10FP2e KSR2, com teor de polímero variando entre 40 e 55% apresentaram padrão de liberação controlada de fármaco no meio anteriormente mencionado. Observou-se cinética de liberação de fármaco de ordem zero para as formulações K4M2 , K100M9, E10FP2 e KSR2. Resultados do teste de similaridade (f 2) para K4M2, E10FP2 e KSR2 foram comparáveis com a formulação de referência K100M9. Gráficos de superfície de resposta também avaliaram o efeito da variável independente sobre as respostas. Estudo de estabilidade foi realizado conforme as diretrizes do ICH e a vida de prateleira calculada foi de 24-30 meses para as formulações K4M2, K100M9 e E10FP2.