Real time release testing of disintegration time of uncoated Tianshu Tablets / 中国中药杂志

In this paper, a real time release testing(RTRT) model for predicting the disintegration time of Tianshu tablets was established on the basis of the concept of quality by design(QbD), in order to improve the quality controllability of the production process. First, 49 batches of raw materials and intermediates were collected. Afterwards, the physical quality attributes of all materials were comprehensively characterized. The partial least square(PLS) regression model was established with the 72 physical quality attributes of raw materials and intermediates as input and the disintegration time(DT) of uncoated tablets as output. Then, the variable screening was carried out based on the variable importance in the projection(VIP) indexes. Moisture content of raw materials(%HR), tapped density of wet masses(D_c), hygroscopicity of dry granules(%H), moisture content of milling granules(%HR) and Carr's index of mixed granules(IC) were determined as the potential critical material attributes(pCMAs). According to the effects of interactions of pCMAs on the performance of the prediction model, it was finally determined that the wet masses' D_c and the dry granules'%H were critical material attributes(CMAs). A RTRT model of the disintegration time prediction was established as DT=34.09+2×D_c+3.59×%H-5.29×%H×D_c,with R~2 equaling to 0.901 7 and the adjusted R~2 equaling to 0.893 3. The average relative prediction error of validation set for the RTRT model was 3.69%. The control limits of the CMAs were determined as 0.55 g·cm~(-3)<D_c<0.63 g·cm~(-3) and 4.77<%H<7.59 according to the design space. The RTRT model of the disintegration time reflects the understanding of the process system, and lays a foundation for the implementation of intelligent control strategy of the key process of Tianshu Tablets.

Diagnostic value of oral glucose tolerance-insulin/C peptide release test in chronic pancreatitis patients with impaired glucose tolerance / 中华胰腺病杂志

Objectives To investigate the value of oral glucose tolerance (OGTT)-insulin/C peptide release test in early diagnosis of chronic pancreatitis (CP)-associated abnormal glucose tolerance.Methods Sixty patients with CP who were admitted to the Department of Gastroenterology,Changhai Hospital from June 2017 to February 2018 were divided into CP with normal glucose tolerance (CP-NGT),CP with impaired glucose tolerance (CP-IGT),CP with newly diagnosed diabetes(CP-new-DM) and CP with the previous history of diabetes (CP-history-DM) according to previous medical records and data from OGTT-insulin/C peptide release test.The characteristics of glucose metabolism,the changes of blood glucose,insulin and C peptide released among the four groups were compared.Results In 43 cases of patients with CP without diabetes,the abnormal glucose metabolism was detected in 6 cases (14.0％) by fasting blood glucose or glycosylated hemoglobin,and in 30 cases (69.8％) by OGTT-insulin/C-peptide release test.The detection rate of abnormal glucose metabolism was increased by 55.8％.In the group of CP-history-DM,the peak secretion of blood glucose,insulin,C peptide was all at 120 min,and the multiplication of increased release of C peptide (peak/baseline) [4.1 (3.4,4.4) vs (6.1 ± 2.2) 、(6.4 ± 2.5)、(6.8 ± 3.8)],the C peptide area under curve (C-PAUC) [(3.6 ± 1.4)]μg · h-1 · L-1 vs 8.6(7.1,9.7),(8.1 ±3.1),(6.9 ±2.7) μg · h-1 L-1] and the homeostasis model of assessment for β cell (HOMA-β) [24.4 (11.4,37.4) vs 52.4 (44.6,92.1),(89.8 ± 57.2),(72.4 ± 57.0)] were all significantly lower,and the difference was statistically significant(all P＜0.05).In the group of CP-new-DM,the peak of blood glucose was at 60 min,while the peak of insulin,C peptide was at 1 20 min,the early insulin secretion index (/ I30/A G30) [2.2 (0.8,4.2)vs (11.4 ± 9.4)] and insulin secretion sensitivity index-2 (ISSI-2) [256.1 (160.1,340.7) vs (548.5 ± 173.2)] in group of CP-new-DM were significantly lower than those in the group of CP-NGT,and the difference was statistically significant (all P ＜0.05).Conclusions The insulin /C peptide secretion was insufficient in the early stage of CP-related diabetes mellitus.Routine OGTT-insulin / C peptide release test for patients with CP can increase the detection rate of abnormal glucose metabolism.

Study on serum insulin and C-peptide release levels of patients with type 2 diabetes mellitus / 国际检验医学杂志

Objective To investigate the changes of postprandial serum insulin and C-peptide concentration of type 2diabetes mellitus (T2DM) patients with different fasting blood glucose concentrations, and to study the islet function of them.Methods There were 492T2DM patients from January 2016to June 2017in our hospital were selected and divided into three groups according to different fasting plasma glucose (FPG) levels:group A, 7.0mmol/L≤FPG＜11.1mmol/L;group B, 11.1mmol/L≤FPG＜14.0mmol/L;group C, FPG≥14.0mmol/L.Meanwhile, 50healthy examinees were collected as the control group.A standard 75g OGTT were performed in 492T2DM patients and 50healthy controls, and 2mL of venous blood of them were collected at 0.5, 1.0, 2.0and 3.0h.The concentration of insulin and C-peptide at each point was measured by chemiluminescence method, and then compared with the control group.Results The concentration of insulin and C-peptide in T2DM patients were slightly higher than those in the control group, but there was no statistical significance (P＞0.05).The serum insulin and C-peptide post-meal in the A, B and C groups and control group increased, but the 1.0hpostprandial blood glucose of control group increased to a peak, and gradually returned to normal at 3.0h;the 2.0hpostprandial blood glucose of A, B and C groups increased to a peak, and decreased at 3.0h, but did not return to normal level.The concentrations of insulin and C-peptide in the A, B and C groups at 0.5, 1.0, and 2.0hpost-meal were significantly lower than those in the control group (P＜0.05).Conclusion The function of isletβcells in T2DM patients decreases with the increase of blood glucose.The determination of insulin and C-peptide can provide a scientific evidence for judging the severity of disease and guiding treatment.

Accelerated Release Testing Method and Preparation of Docetaxel Capsule Tension Ring / 中国药学杂志

OBJECTIVE: To develop the accelerated release test method of docetaxel capsule tension ring and optimize its formulation. METHODS: The effects of ethanol concentration in the medium (0%, 5%, 10%) and temperature (37 and 45 ℃) on the release rate of docetaxel capsule tension ring were investigated, and the correlation regression equation between the accelerated release rate and the long-term release was established. Then, the best prescription was screened out with the accelerated release test method. RESULTS: The drug release rate of these preparations could be increased by four times under the accelerated conditions, i.e., using pH 7.4 phosphate buffer solution containing 5% ethanol as the release medium and operating at (45±0.5)℃. The accelerated release and long-term release were fitted the best using binomial model (y=0.004 6x2+0.437 4x+9.683 7, r2=0.998 4). The preparation using PLGA5050 (60K-100K=1:1, W/W) with drug-loading of 30% released drug stably and sustainedly for 30 d, and its release behavior was consistent with Peppas equation drug release model. CONCLUSION: Accelerated release testing can be employed as a rapid screening test to facilitate the formulation optimization of docetaxel capsule tension ring. This preparation has been proven to have sustained-release characteristics, suggesting a good clinical application prospect.

Explore the occurrence and development of β cell dysfunction and insulin resistance according to the stratification on normal glucose tolerance / 中华内分泌代谢杂志

After the stratification of the normal glucose tolerance, the changes of insulin resistance and βcell function in the development of type 2 diabetes mellitus were investigated. A retrospective analysis on data of 275 cases with oral glucose insulin releasing tests. The area under the insulin curve (AUCINS ) 108. 43 mU/ L was taken as the critical value of diagnosis. Normal glucose tolerance subjects were divided into the NGT-a group(AUCINS<108. 43 mU/ L) and the NGT-b group(AUCINS≥108. 43 mU/ L). The plasma glucose, insulin, insulin sensitivity, and β cell function were compared among the 4 groups: NGT-a group (n=96), NGT-b group (n=49), prediabetes group (n=71), and type 2 diabetes mellitus group ( n = 59). Among the fasting insulin, 2 h insulin, AUCINS , early-phase insulin secretion index(△I30 / △G30), the ratio of total insulin area under curve, and total glucose area under curve, disposition index, homeostasis model assessment for insulin resistance, and Matsuda insulin sensitivity index, the relationship as follows: NGT-b group>prediabetes group>NGT-a group>type 2 diabetes mellitus group. The NGT-b group was always the highest, prediabetes group was lower, NGT-a group and type 2 diabetes mellitus group were the lowest, there were significant differences (all P<0. 05). Making the NGT-a group as the basic state, in the NGT-b group, β cell function has begun to appear compensation and insulin resistance, and β cell function compensation reached the peak, the β cell function in the prediabetes group was beginning to compensate for the deficiency, the function of β cell in type 2 diabetes mellitus group decreased further. These findings suggest that the development process of type 2 diabetes mellitus could be the following four stages according to the function of β cell: β cell function normal, β cell functional compensation, β cell function loss of compensation, and finally β cell function failure.

Explore the occurrence and development of β cell dysfunction and insulin resistance according to the stratification on normal glucose tolerance / 中华内分泌代谢杂志

After the stratification of the normal glucose tolerance, the changes of insulin resistance and βcell function in the development of type 2 diabetes mellitus were investigated. A retrospective analysis on data of 275 cases with oral glucose insulin releasing tests. The area under the insulin curve (AUCINS ) 108. 43 mU/ L was taken as the critical value of diagnosis. Normal glucose tolerance subjects were divided into the NGT-a group(AUCINS<108. 43 mU/ L) and the NGT-b group(AUCINS≥108. 43 mU/ L). The plasma glucose, insulin, insulin sensitivity, and β cell function were compared among the 4 groups: NGT-a group (n=96), NGT-b group (n=49), prediabetes group (n=71), and type 2 diabetes mellitus group ( n = 59). Among the fasting insulin, 2 h insulin, AUCINS , early-phase insulin secretion index(△I30 / △G30), the ratio of total insulin area under curve, and total glucose area under curve, disposition index, homeostasis model assessment for insulin resistance, and Matsuda insulin sensitivity index, the relationship as follows: NGT-b group>prediabetes group>NGT-a group>type 2 diabetes mellitus group. The NGT-b group was always the highest, prediabetes group was lower, NGT-a group and type 2 diabetes mellitus group were the lowest, there were significant differences (all P<0. 05). Making the NGT-a group as the basic state, in the NGT-b group, β cell function has begun to appear compensation and insulin resistance, and β cell function compensation reached the peak, the β cell function in the prediabetes group was beginning to compensate for the deficiency, the function of β cell in type 2 diabetes mellitus group decreased further. These findings suggest that the development process of type 2 diabetes mellitus could be the following four stages according to the function of β cell: β cell function normal, β cell functional compensation, β cell function loss of compensation, and finally β cell function failure.

Value of γ-interferon release test in the diagnosis of entry-exit people with tuberculosis / 国际检验医学杂志

Objective To investigate the clinical significance of γ-interferon release test (IGRA) in the diagnosis of entry-exit people with tuberculosis.Methods A total of 64 patients with tuberculosis and 46 healthy people were detected by IGRA,tuberculin skin test (TST),LAM,38× 103 and 16 × 103.The results of different methods were compared and analyzed.Results The sensitivity of IGRA detection method (88.9 ％) and specificity (95.8 ％) were both higher,while the sensitivity (92.7 ％) of the TST method was higher and the specificity (76.7 ％) was lower.Conclusion The sensitivity and specificity of IGRA in the detection of tuberculosis are higher,and it has important clinical application value.

Optimizing the method in calculating the insulin dosages in the insulin hypoglycemia-growth hormone stimulation test:preliminary exploration / 中华内分泌代谢杂志

Objective To explore more suitable calculation method of the insulin dosage in insulin hypoglycemia-growth hormone stimulation test(insulin tolerance test, ITT). Methods Fifty-six subjects suspected of growth hormone deficiency were divided into primary and secondary onset groups. All the patients took oral glucose tolerance test and ITT. Homeostasis model of assessment for insulin resistance index ( HOMA-IR) and insulin sensitivity index ( ISI), area under insulin curve ( AUCINS ) and the area under glucose curve ( AUCPG ) were calculated. The insulin dosages during ITT between two groups were compared and the main factors influencing the insulin dosage were analyzed. Results There was no difference in the insulin dosage during ITT between primary and secondary groups. The actual dosage of insulin in this cohort study revealed a significant difference from the initial insulin dosage recommended by the guideline. Multiple linear regression analysis found that AUCINS and body mass index were the independent factors affecting the insulin dosage. Then the optimized coefficient of ITT ( γ) were found. Conclusion The insulin dosage used in our study was inconsistent with the guidelines-recommended ones. In order to make ITT more efficient and safer, a more optimized calculation method to improve the successful rate of insulin-induced hypoglycemia in ITT is proposed.

Comparison of the Commercial QuantiFERON-CMV and Overlapping Peptide-based ELISPOT Assays for Predicting CMV Infection in Kidney Transplant Recipients

Cytomegalovirus (CMV) is one of the most important opportunistic infections in transplant recipients. Tests for CMV-specific T cell responses have been proposed to change the current risk stratification strategy using CMV assays. We evaluated the usefulness of pre-transplant CMV-specific T cell assays in kidney transplant (KT) candidates for predicting the development of CMV infection after transplantation comparing the results of the overlapping peptides (OLPs)-based enzyme-linked immunospot (ELISPOT) assay and the commercial QuantiFERON-CMV assay. We prospectively enrolled all cases of KT over a 5-month period, except donor CMV-seropositive and recipient seronegative transplants that are at highest risk of CMV infection. All the patients underwent QuantiFERON-CMV, CMV OLPs-based pp65, and immediate-early 1 (IE-1)-specific ELISPOT assays before transplantation. The primary outcome was the incidence of CMV infection at 6 months after transplant. The total of 47 KT recipients consisted of 45 living-donor KTs and 2 deceased-donor KTs. There was no association between positive QuantiFERON-CMV results and CMV infection. However, 10 of 34 patients with phosphoprotein 65 (pp65)- or IE-1-specific ELISPOT results higher than cut-off value developed CMV infections compared with none of 13 patients with results lower than cut-off value developed CMV. The OLPs-based ELISPOT assays are more useful than the QuantiFERON-CMV assay for predicting CMV infection. Patients with higher CMV-specific T cell immunity at baseline appear to be more likely to develop CMV infections after KT, suggesting that the abrupt decline in CMV-specific T cell responses after immunosuppression, or high CMV-specific T cell responses due to frequent CMV activation before KT, may promote CMV infection.

The value of quantitative TB-DNA test,interferon gamma release test,tuberculosis antibody detection in the pulmonary tuberculosis smear positive patients / 国际检验医学杂志

Objective To investigate the value of quantitative TB‐DNA test ,interferon gamma release test and the detection of tuberculosis antibodies for the diagnosis of active pulmonary tuberculosis .Methods 51 patients were diagnosed as tuberculosis from 2013 July to 2014 June in the hospital ,whose sputum smear microscopy for acid fast bacilli were positive .Then TB‐DNA quantitative test ,interferon gamma release test (T‐SPOT .TB)and tuberculosis antibody detection were performed for those pa‐tients .All the result were retrospectively analysed .Results The positive rate of T‐SPOT .TB was 90 .1% ,the positive rate of quan‐titative TB‐DNA test was 74 .5% and the positive rate of tuberculosis antibody detection was 37 .3% .Conclusion Because the re‐sult of T‐SPOT .TB is not affected by the process of specimen collection ,it is the most sensitive test of the three tests at present , and has higher value in the auxiliary diagnosis of active pulmonary tuberculosis than the other two .

La utilidad de la reacción tuberculina / The usefulness of the tuberculin skin test

Tuberculin skin test (TST) is a test based on purified protein derivative of Mycobacterium tuberculosis (or PPD). TST has been considered a standard for identifying tuberculous infected people by the World Health Organization (WHO) since 1955. However, other immunological tests that measure the interferon gamma production(Interferon gamma release assays or IGRAs) in the individual`s cells with latent tuberculosis (TB) infection (LTBI) have been used as surrogate TST, despite having certain restrictions. WHO has made several recommendations for preventive treatment in cases of LTBI aiming to supplant the universal shortage of PPD since 2014. Some rules for identifying LTBI individuals without the TST still reiterate the importance of this test in many countries.

La reacción tuberculina (RT) es una prueba cutánea que emplea el derivado proteico purificado de Mycobacterium tuberculosis o PPD. Desde 1955 ha sido considerada estándar para identificar personas infectadas por el bacilo de la tuberculosis por la Organización Mundial de la Salud (OMS). Sin embargo, otras pruebas inmunológicas que miden la producción de interferon gama (IGRAs) por las células del individuo con infección latente de TB (ILTB) se han empleado como sucedáneas de la RT, a pesar de presentar ciertas restricciones. La OMS ha hecho diversas recomendaciones para la conducta preventiva en casos de ILTB que de alguna forma buscan suplantar la falta universal de PPD desde 2014. Algunas perspectivas de identificar personas con ILTB sin contar con el PPD reiteran todavía la importancia de la RT en muchos países.

Application of microcolumn gel technology in detection of neonatal hemolytic disease / 国际检验医学杂志

Objective To investigate the application value of microcolumn gel technology in screening hemolytic disease of the newborns(HDN) .Methods The direct antiglobulin test(DAT) ,antibody release test and free antibody test were performed in 212 cases of suspected HDN in our hospital by using microcolumn gel assay .Results In 212 cases of suspected HDN ,50 cases(23 .6% ) were diagnosed as HDN ,including 45 cases (21 .2% ) of ABO‐HDN and 5 cases (2 .4% ) of Rh‐HDN .In 45 cases of ABO‐HDN ,23 cases (36 .5% ) were A blood type and 22 cases (28 .2% ) were B blood type .The sensitivity of antibody release test ,DAT and free antibody test was 100% ,28% and 92% respectively .Conclusion The microcolumn gel technology can detect HDN fastly and accu‐rately ,with the advantages of simple operation ,less sample consumption ,high sensitivity and specificity ,which can provide reliable basis for HDN diagnosis and is worth popularizing and applying in clinic .

Analysis of test results of ABO hemolytic disease of newborn in Chizhou area / 国际检验医学杂志

Objective To understand the laboratory testing current situation of ABO hemolytic disease of the newborn(ABO-HDN)in Chizhou area,and to analyze the test results of serological three indexes tests in order to provide the basis for clinical diag-nosis.Methods The ABO blood group identification and serological three indexes tests(direct antiglobulin test,free antibody test, antibody release test)were performed by using microcolumn gel method.Results A,B,O and AB blood groups were 29.13%, 31.09%,37.82% and 1.96%;the total positive rate of ABO-HDN was 22.41%(80/357),the positive rates of ABO-HDN in A and B blood groups were 38.46% (40/104)and 36.04% (40/111 )respectively;the occurrence rate of ABO-HDN had no statistical difference between blood group A and B (P >0.05);the positive rates of the direct antiglobulin test,free antibody test and antibody release test were 1.96%(7/357),4.76%(17/357)and 22.41%(80/357)respectively.Conclusion The serological three indexes tests are the main basis for the diagnosis of ABO-HDN,the antibody release test shows the highest positive rate.If clinically consid-ering HDN,the newborns should conduct the ABO-HDN screening as early as possible for clarifying the diagnosis and performing the early treatment.

Pesquisa de infección tuberculosa latente en personal de la salud en cuatro instituciones de salud en Santiago de Chile / Latent tuberculosis infection screening in healthcare workers in four large hospitals in Santiago, Chile

Background: It is currently unknown which is the prevalence of latent tuberculosis infection in healthcare workers in Chile, but this group has been described as at higher risk of developing active tuberculosis than general population. Objectives: To determine the prevalence of latent tuberculosis infection in a sample of healthcare workers from at risk areas. Methodology: A cross-sectional, descriptive study, conducted in health care workers from clinical laboratories or respiratory care areas in four hospitals in Santiago. Latent tuberculosis infection detection was determined by Quantiferon® TB Gold In Tube testing (QFT). Results: QFT resulted positive in 20 of 76 (26.3%) of the individuals tested. Test positivity reached 62.5% among the personnel that reported history of past TB contact in the community, 50% among the personnel who belonged to the national tuberculosis control program and 38% among those doing induced sputum, acid fast smear or mycobacterial cultures. The proportion of individuals with positive QFT was significantly lower in those personnel who had no such risk factors (15.7%, p = 0.03). The proportion of latent tuberculosis infection also increased in direct relation to the age of the subject. Conclusion: Latent tuberculosis infection as detected by QFT testing was highly prevalent in healthcare workers included in the present study. Further exploring the limitations and possible scenarios for this new diagnostic tool is needed, with emphasis on health personnel at higher-risk and younger individuals.

Introducción: Se desconoce en la actualidad cuál es la real prevalencia de infección tuberculosa latente en el personal de salud en Chile; sin embargo, este grupo ha sido descrito como con mayor riesgo de desarrollar tuberculosis activa que la población general. Objetivo: Determinar la prevalencia de infección tuberculosa latente en funcionarios de la salud en diferentes áreas laborales de riesgo. Metodología: Estudio de corte transversal, descriptivo, realizado en funcionarios pertenecientes a laboratorios clínicos o áreas de atención broncopulmonar de cuatro hospitales de la Región Metropolitana en quienes se hizo test de Quantiferon TB Gold®In tube(QFT). Resultados: Se evidenció infección tuberculosa latente en 20 de las 76 (26,3%) personas estudiadas. En aquellos funcionarios que referían antecedente de contacto en el pasado en la comunidad con enfermos de tuberculosis, la positividad del test llegó a 62,5%; en aquellos que pertenecían al Programa Nacional de Control de la Tuberculosis, a 50% y en los que realizaban toma de esputo inducido, baciloscopias o cultivo de micobacterias, a 38%. La proporción de individuos con QFT positivo fue significativamente menor en aquellos funcionarios que no tenían estos antecedentes (15,7%, p = 0,03). Se encontró además una mayor proporción de infección tuberculosa latente a mayor edad del individuo estudiado. Conclusión: La infección tuberculosa latente medida por QFT resultó altamente prevalente en el personal de la salud incluido en el presente estudio. Es necesario seguir profundizando en los posibles escenarios de implementación y limitaciones del uso de esta nueva herramienta diagnóstica, haciendo énfasis en el personal de la salud de mayor riesgo y menor edad.

Diagnosis and treatment of latent tuberculosis infection

Tuberculosis (TB) is still an important cause of morbidity and mortality worldwide. Nearly one-third of the world's population is latently infected with Mycobacterium tuberculosis, and 10% of them will develop active TB during their lifetime. The tuberculin skin test or interferon-gamma release assay (IGRA) is the method for diagnosis of latent TB infection. Although commercially available IGRAs have limitations in serial testing, and testing children and immunosuppressive patients, IGRAs have superior sensitivity and specificity compared with conventional tuberculin skin testing, especially in Bacillus Calmette-Guerin vaccinated populations. For the treatment of latent TB infection, 9 months isoniazid is the standard treatment in Republic of Korea. However, shorter treatment regimens, including 4 months of rifampin, 3 months of isoniazid/rifampin, and once weekly isoniazid/rifapentine are currently alternatives. Identification and treatment of latent TB infection has lowered the TB incidence in developed countries. Therefore, for TB control, diagnosis and treatment of latent TB infection is important. However, there is lack of research on latent TB infection in South Korea. To revise the guideline, a large prospective trial on the treatment of latent TB infection is needed.

In vitro release of diclofenac diethylamine from gels: evaluation of generic semisolid drug products in Brazil

In order for the pharmacological action of a topical dermal drug product to occur, the drug must first be released from the vehicle to be available to penetrate the skin layers and reach the site of action. Drug release is mainly dependent on the characteristics of the formulation. Currently, to register a generic or a similar drug product in Brazil performance testing of topical drug products for local action is not required. In this context, this aim of this study was to evaluate the in vitro release of commercial diclofenac diethylamine gel products available on the Brazilian pharmaceutical market, using the vertical diffusion cell method. Factors which may influence the test, such as the type of membrane used, and the effect of the formulation characteristics on the diffusion rate were evaluated. Brazilian legislation currently allows generic drug products to contain excipients other than the reference drug, which may affect the drug release from the vehicle. Only one of the four generic drug products tested could be considered equivalent to the reference Cataflam Emulgel®. The cellulose acetate and polyethersulfone membranes tested were found to be interchangeable in the in vitro release studies carried out on this product.

Para exercer ação farmacológica, medicamentos tópicos de aplicação cutânea precisam, primeiramente, liberar o fármaco do veículo, para que desta forma ele se torne disponível para penetração nas camadas da pele, até atingir seu local de ação. A liberação do fármaco do veículo depende principalmente das características da formulação. Até a presente data, para registrar um medicamento genérico ou similar no Brasil não se exigem testes de desempenho para produtos tópicos de ação local. O presente trabalho teve como objetivo avaliar a liberação in vitro de especialidades farmacêuticas de diclofenaco dietilamônio gel do mercado farmacêutico brasileiro, usando o sistema de célula de difusão vertical. Avaliaram-se fatores que influenciam o teste como o tipo de membrana usada nos ensaios de liberação e características da formulação que impactam a velocidade de difusão. A legislação vigente no País permite que medicamentos genéricos contenham excipientes diferentes do medicamento referência. Esta diferença afetou a liberação do fármaco do veículo. Dos quatro medicamentos genéricos testados apenas um seria considerado equivalente ao medicamento referência Cataflam Emulgel®. As membranas de acetato de celulose e polietersulfona testadas apresentaram-se intercambiáveis nos estudos de liberação desse produto.

Analysis of insulin release pattern in patients with polycystic ovary syndrome and normal glucose tolerance / 中华内分泌代谢杂志

Objective To investigate the release pattern of insulin after the load of glucose in patients with polycystic ovary syndrome ( PCOS ) and normal oral glucose tolerance.Methods Sixty-three patients with PCOS were undertaken oral glucose tolerance test (OGTT) and insulin release test,while 34 women with normal menstrual cycle served as control.Results Among 63 patients with PCOS,33 cases were obese with body mass index over 25 kg/m2,including 5 with abnormal OGTT.All 30 non-obese patients with PCOS had normal OGTT.The prevalences of insulin resistance were 78.8％,16.7％,and 9.0％ in obese PCOS,non-obese PCOS,and control groups,respectively.Abnormal insulin release curve were found in 84.5％,70.0％,and 14.7％ of subjects in these 3 groups,respectively.In 58 PCOS patients with normal OGTT,the prevalence of insulin resistance was 44.8％,and 75.9％with abnormal insulin release curve. Among them,body mass index of 32 patients,whose homeostasis model assessment for insulin resistance (HOMA-IR) and fasting insulin remained in normal range,was similar to those of control group [ ( 20.52 ± 2.86 vs 20.01 ± 2.54 ) kg/m2,P＞0.05].Conclusion These findings indicate that insulin release test is useful in detecting insulin resistance.Insulin release is elevated in PCOS patients even with normal OGTT.

Emulsões O/A contendo Cetoconazol 2,0%: avaliação da estabilidade acelerada e estudos de liberação in vitro / O/W Emulsion Containing 2.0% Ketoconazole: Accelerated Stability Test and in vitro Release

Os objetivos do estudo foram desenvolver e avaliar a estabilidade físico-química de emulsões O/A contendo cetoconazol a 2,0% e determinar seu perfil de liberação in vitro. As formulações foram preparadas com bases auto-emulsionáveis com diferentes características químicas. A estabilidade do sistema foi avaliada de acordo com o Guia para Realização de Testes de Estabilidade em Produtos Farmacêuticos, utilizando diferentes temperaturas (4ºC, 37ºC e 45ºC) por um período de tempo de três meses. Os parâmetros avaliados durante o ensaio foram: as características organolépticas,o pH, o comportamento reológico e a concentração do ativo. A emulsão considerada estável foi submetida ao ensaio de liberação in vitro utilizando célula de difusão de Franz. A quantificação do cetoconazol na formulação e na solução receptora foi realizada por método espectrofotométrico no ultravioleta a 244 nm. Dentre as formulações testadas, somente aquela preparada com álcool cetoestearílico e estearato de polietilenoglicol (PEG20) manteve suas características físico-químicas estáveis durante o teste. O estudo de liberação in vitro demonstrou que o fármaco foi liberado do sistema gradualmente no decorrer do tempo, apresentando uma cinética pseudo zero ordem.

The goal of this work was to develop and assess the physicochemical stability of O/W emulsions containing 2.0% ketoconazole and to determine their in vitro release profile. These formulations were prepared with self-emulsifying bases that differed in their chemical characteristics. The stability of the system was assessed, as recommended in the Guide to Drug Product Stability Tests, over 3 months at 3 different temperatures (4ºC, 37ºC and 45ºC). The characteristics assessed during the test were the organoleptic properties, pH, rheological behavior and drug concentration. The most stable emulsion was subjected to an in vitro release test in a Franz diffusion cell system. The ketoconazole in both the formulation and receptor phase was determined by UV spectrophotometry at 244 nm. The O/W emulsion prepared with cetearyl alcohol and polyethylene glycol (PEG20) stearate was the only one that maintained its physicochemical characteristics throughout the test. The in vitro release test demonstrated that the drug was released gradually, exhibiting pseudo zero-order kinetics.

Preparation of Collagen Modified Hyaluronan Microparticles as Antibiotics Carrier

Hyaluronan (HA), a natural glycoaminoglycan featuring an extracellular matrix, has been suggested as an effective biocompatible material. In this study, the effectiveness of HA microparticles as a carrier system for antibiotics was evaluated, and their physicochemical characteristics were determined. Microparticles were fabricated by the gelation of sulfadiazine (SD) loaded HA solution with calcium chloride through either a granulation (GR-microparticles) or encapsulation (EN-microparticles) process, and atelocollagen was incorporated into the microparticles as an additive in order to improve their physical properties. The characteristics of the microparticles were examined by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and swelling test. In vitro release experiments were performed for 7 days and the released amount of SD was determined using high-performance liquid chromatography (HPLC). Microscopic observations revealed that the collagen incorporated HA particles had a more compact surface than the HA particles. DSC analysis determined a loss of SD crystallinity in the particles. Calcium chloride retarded the swelling of particles, whereas the loaded drug contents did not affect this property. Both GR-and EN-microparticles sustained SD release with initial bursting effect. SD release from EN-microparticles was faster than from GR- microparticles. In addition, the release rate was dependent on the SD content in the microparticles. These results suggest that collagen modified HA microparticles have a potential as a release rate controlling material for crystalline drugs such as SD.