ABSTRACT
Ainda que não exista previsão legal, crianças e adolescentes vivenciam o processo de dissolução da adoção. Na literatura, a vivência subjetiva de crianças e adolescentes frente ao fenômeno tem sido pouco abordada. O presente estudo objetivou conhecer as vivências de crianças e adolescentes que retornaram ao acolhimento após a adoção, além de compreender sua percepção sobre família e as expectativas sobre o futuro. Realizou-se uma pesquisa qualitativa exploratória com três crianças e uma adolescente em uma instituição de acolhimento da região metropolitana de Porto Alegre/RS. Os dados obtidos em entrevistas semiestruturadas e hora do jogo foram examinados por meio de análise temática. Os resultados foram agrupados em quatro temáticas: 1) concepções de família; 2) experiência de adoção; 3) experiências de retorno ao acolhimento; 4) perspectivas de futuro. Identificou-se que as crianças idealizam a família nuclear, amorosa, e avaliam que a decisão de retorno para o acolhimento foi delas, embora suas perspectivas de futuro sejam centradas na expectativa de uma nova adoção. Constatou-se que a experiência de adoção e retorno para o acolhimento é permeada de sofrimento, o que demanda a criação de políticas públicas de atenção a crianças e adolescentes nesse contexto.
Although there is no legal provision, children and adolescents experience the process of adoption dissolution. In the literature, little is discussed about the subjective experience of children and adolescents who face this experience. The present study aimed at investigating the experiences of children and adolescents who returned to the foster care system after being adopted and understanding their perceptions about family and future expectations. An exploratory qualitative study was carried out with three children and one teenager in a foster care institution located in the metropolitan area of Porto Alegre/RS. The data obtained from semi-structured interviews and play were examined through thematic analysis. The results were grouped into four themes: 1) conceptions of family; 2) adoption experience; 3) experiences of returning to the foster system; 4) expectations for the future. It was identified that the children idealize the nuclear and loving family, and thought of their return to the system as their own decision, although their future expectations revolve around being adopted again. It was found that the experience of adoption and subsequent return to the foster system is marked by suffering, which demands the implementation of public policies for the care of children and adolescents in this context.
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Determine the efficacy of 5 % chlorine dioxide as an endodontic irrigant for pulp dissolution. Thirty five samples of human dental pulp were obtained, previously weighed and immersed in three solutions= 5 % ClO 2, 5.25 % NaOCl and saline (control group), for 10 minutes at 32 ºC; they were dried and reweighed. Then the weight loss was compared to the original weight and analyzed statistically. 5.25 % NaOCl and 5 % ClO 2 dissolved the dental pulp samples more effectively than saline (p> 0.001). No statistically significant difference was found between the tissue dissolving proper ties of 5.25 % NaOCl and 5 % ClO2 (p=0.893). 5 % ClO2 is effective in dissolving human dental pulp tissue.
El objetivo de este estudio fue determinar la eficacia del dióxido de cloro al 5 % como irrigante endodóntico para la disolución pulpar. Se obtuvieron 35 muestras de pulpa dental humana, se pesaron previamente y se sumergieron en tres soluciones= 5 % ClO2, 5.25 % NaOCl y suero fisiológico (grupo control), durante 10 minutos a 32ºC; se secaron y se pesaron de nuevo. Luego se comparó la pérdida de peso del peso original y se analizó estadísticamente. NaOCl al 5.25 % y ClO2 al 5 % disolvieron las muestras de pulpa dental con más eficacia que el suero fisiológico (p> 0.001). No se encontró diferencias estadísticamente significativas entre las propiedades de disolución de tejido de NaOCl al 5.25 % y ClO2 al 5 % (p=0.893) ClO2 al 5 % es eficaz para disolver tejido de pulpa dental humana.
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Buccal tablets
Diclofenac sodium
Drug release
Mucoadhesion
Mucoadhesive tablets
Release kinetics
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Abstract Albendazole is an anthelmintic drug commonly used in parenchymal neurocysticercosis and cystic echinococcosis. The aim of this study was to explore whether disparities in the dissolution profiles of albendazole products lead to significant differences in pharmacokinetic parameters. Three generic products and the innovator were evaluated in vitro. Quality control tests were performed, and dissolution profiles were obtained according to the Mexican Pharmacopeia. Although all products passed the quality control tests, none of the generic products complied with the similarity factor (f 2). The product with the lowest f 2 value in respect to the reference was chosen for in vivo evaluation. The study was carried out in 12 healthy volunteers who received 400 mg of the generic or reference product according to a crossover design. No significant differences were found in Cmax and AUC for albendazole and its main metabolite, albendazole sulfoxide, between products. Two absorption peaks were observed in the pharmacokinetic profile, and a population (22%) with different absorption rates and delay time for the the second peak was found. Based on the results, due to the high variability in the absorption process the differences observed in vitro could not be observed in vivo.
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The properties of dry-coated paracetamol particles(fast-dissolving model drug)with carnauba wax particles as the coating agent(dissolution retardant)were investigated.Raman mapping technique was used to non-destructively examine the thickness and homogeneity of coated particles.The results showed that the wax existed in two forms on the surface of the paracetamol particles,forming a porous coating layer:i)whole wax particles on the surface of paracetamol and glued together with other wax surface particles,and ii)deformed wax particles spread on the surface.Regardless of the final particle size fraction(between 100 and 800 μm),the coating thickness had high variability,with average thickness of 5.9±4.2 μm.The ability of carnauba wax to decrease the dissolution rate of paracetamol was confirmed by dissolution of powder and tablet formulations.The dissolution was slower for larger coated particles.Tableting further reduced the dissolution rate,clearly indicating the impact of subsequent formulation processes on the final quality of the product.
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@#Separation issues have been rampant, and a significant rise in union dissolution cases in the Philippines has been observed. This certain occurrence should be given particular attention because it may alter the individual's way of living, particularly in perceiving and dealing with relationships. This study explores the lived experience of individuals who have undergone parental separation. The study utilized a Hermeneutic Phenomenological Design, which involved ten (10) respondents using a semi-structured key informant interview guide. The respondents were selected based on criteria as follows: (1) Have parents who have decided on the dissolution of marriage (annulled or informal) living separately; (2) 18 years of age and above; (3) Residents of Central Visayas; permanent or transient in Cebu City and; (4) Able to understand and express ideas in Cebuano dialect or English language. An Interpretative Phenomenological Analysis anchored on van Manen's six-step interpretive phenomenological approach with management and analysis done manually created a poem titled “Memoirs of Yesterday,” which incorporates three (3) major themes: (1) Into the Tunnel: Etiology of Separation, (2) The Darkness in the Tunnel: effects of the dissolution of marriage to children- emotional, psychological and academic status and (3) The Light After the Tunnel: attitude of the child and parent towards relationships and separation. The study implies that nurses should recognize the importance of assessing family concerns in rendering holistic and individualized client care. Thus, nurses should use assessed needs in advocating for the creation of more programs on awareness and counseling to families and, most especially, children.
Subject(s)
Hermeneutics , Surveys and QuestionnairesABSTRACT
Objective:To compare the effect and biotoxicity of tert-butyl acetate (TBA) and ethyl butyrate (EB) on stone dissolution in vitro.Methods:Ten gallstone samples from patients with multiple gallbladder stones were selected and the cholesterol content was analyzed by HPLC. Stone dissolution tests of TBA and EB were performed on cholesterol gallstone in vitro, and the weight of stone at each time point was recorded, meanwhile, methyl tert-butyl ether (MTBE) was used as the control. The inhibitory effects of MTBE, TBA and EB on proliferation of human normal liver cell line LO2 were analyzed by cell proliferation inhibition assay. Flow cytometry was used to analyze the effects of MTBE, TBA and EB on the early and late apoptosis of LO2 cells, and the changes of reactive oxygen species level in LO2 cells were also analyzed.Results:Of the 10 gallbladder gallstones, 6 were cholesterol gallstones and 4 were non-cholesterol gallstones. Stone dissolution experiment showed that the remaining stones of MTBE, TBA and EB groups were (47.83±3.84)%, (58.12±4.53)% and (75.75±4.61)% 30 minutes later. The remaining stones were (18.38±6.47)%, (33.82±6.22)% and (56.38±3.91)% 90 minutes later. MTBE had the best stone dissolution effect in vitro, the stone dissolution effect of TBA was slightly weaker than MTBE, and the stone dissolution effect of EB was relatively weak in all ( P<0.05). The cell proliferation inhibition experiment showed that the cell viability of the control group, MTBE group and TBA group were (100.00±4.46)%, (96.79±4.32)% and (93.72±3.51)%, respectively, and there were no significant differences among the three groups ( P>0.05). However, the cell viability of EB group (87.57±5.29)% was lower than the above three groups, and the differences were statistically significant ( P<0.001). The early apoptosis and late apoptosis of the control group were (1.67±0.15)% and (1.27±0.06)%, respectively. EB induced early apoptosis (15.90±0.53)% ( P<0.001) and late apoptosis (5.13±0.76)% ( P<0.05). However, MTBE and TBA had no significant effect on cell apoptosis ( P>0.05). Compared with control group, MTBE, TBA and EB all significantly inhibited the level of reactive oxygen species ( P<0.05), and the inhibitory effect of EB was the most obvious. Conclusions:TBA has good stone dissolution effect and biosafety for gallbladder cholesterol stones in vitro, while EB has relatively poor performance. TBA is a potential drug for gallstone dissolution.
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Objective To establish a near infrared (NIR) quantitative model for the dissolution behavior of aripiprazole tablets. Methods The NIR spectra of aripiprazole tablets were collected and the dissolution tests were performed to determine the dissolution of each tablet at 3, 6, 9, 12, 15 and 30 min. The near infrared spectra regions of 4 000.00-4 396.90, 5 326.43-12 000.00 cm−1 were pretreated by Savitzky-Golay smoothing filter, and the dissolution behavior model was established by partial least squares method. Results The root mean square error of calibration (RMSEC) and the root mean square error of prediction (RMSEP) at different time points were analyzed. RMSEP was lower than 8%. The calibration correlation coefficient (RC) and the prediction correlation coefficient (RP) at different time points were above 0.95 (except for the point of 6 min). There was a good correlation between the NIR spectrum and the dissolution at each time point. Conclusion NIR spectroscopy could predict the dissolution behavior of aripiprazole tablets, which lays a foundation for online quality monitoring of tablets by NIR spectroscopy.
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@#In order to guarantee the quality of traditional Chinese medicines (TCMs), the crystallization transformation of complex extracts of TCMs and the influence of solid form on their physicochemical properties were studied.The extract of total flavonoids from Pueraria lobata was taken as a model.Crystallization transformation happened when lofting under different conditions, and the intrinsic dissolution tests were carried out.It was found that humidity was the key factor to induce crystallization of total flavonoids from Pueraria lobata.The greater the wettability was, the more the crystallization was.The dissolution rate of total flavonoids from Pueraria lobata with the most crystallization amount significantly decreased by 96.51% compared to the sample without crystallization.After further simulating the preparation process of total flavonoids from Pueraria lobata, it was found that the wet granulation process with introduced water would also lead to crystallization and reduced dissolution rate.As for all crystallization samples, there was an inversely proportional relationship between the dissolution rates and the amount of crystallization.The risk of crystallization existed both in the storage and preparation process of TCM extracts.Crystallization would significantly affect the dissolution rate, and thus the quality of TCM products.In this study, the crystallization transformation of amorphous complex TCM extracts was discovered, and the effect of the crystallization transformation on its dissolution behavior was systematically studied, which provides a new research idea for assuring the quality of TCM products and promoting the improvement of TCM preparation level.
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In this paper, 50 batches of representative traditional Chinese medicine tablets were selected and the disintegration time was examined with the method in Chinese Pharmacopoeia. The disintegration time and disintegration phenomenon were recorded, and the dissolution behaviors of water-soluble and ultraviolet-absorbent components during the disintegration process of tablets were characterized by self-control method. The results revealed that coating type and raw material type influenced the disintegration time of tablets. It was found that only 4% of traditional Chinese medicine tablets had obvious fragmentation during the disintegration process, while 96% of traditional Chinese medicine tablets showed gradual dissolution or dispersion. Furthermore, according to the disintegration speed, disintegration phenomenon, and whether the cumulative dissolution of measured components was > 90% at complete disintegration, a disintegration behavior classification system(DBCS) was created for the regular-release traditional Chinese medicine tablets. As a result, the disintegration behaviors of 50 batches of traditional Chinese medicine tablets were classified into four categories, i.e. ⅠA_2, ⅠB_1, ⅡB_1, and ⅡB_2. traditional Chinese medicine tablets(Class I) with disintegration time ≤ 30 min were defined to be rapid in disintegration, which can be the objective of optimization or improvement of Chinese herbal extract(semi extract) tablets. Different drug release models were used to fit the dissolution curve of traditional Chinese medicine tablets with gradual dissolution or dispersion phenomenon(i.e. Type B tablets). The results showed that the dissolution curves of water-soluble components in the disintegration process conformed to the zero order kinetics and the Ritger-Peppas model. It could be inferred that the disintegration mechanisms of type B tablets were a combination of dissolution controlled and swelling controlled mechanisms. This study contributes to understanding the disintegration behavior of traditional Chinese medicine tablets, and provides a reference for the design and improvement of disintegration performance of traditional Chinese medicine tablets.
Subject(s)
Commerce , Medicine, Chinese Traditional , Tablets , Water , Drug CompoundingABSTRACT
Abstract The aim of this study was to compare the dissolution properties of ibuprofen solid oral dosage forms commercially available in Bosnia and Herzegovina and to estimate the influence of dissolution medium composition on the drug release. Eight products (A-H) were subjected to in vitro dissolution test using experimental conditions described in USP42-NF37. Dissolution properties of one selected product were examined in the presence of alcohol (22.2% v/v) and fruit juice (22.2% v/v). Products marked B-H complied with the pharmacopeial criteria. Dissolution profile of product B was similar with dissolution profiles of products D, E, F and G and similarity was also found between products A-D, C-G, D-G and E-F. Drug release from most of the examined preparations fitted best to the Weibull kinetic model. In the presence of alcohol in the medium, higher amount of ibuprofen was dissolved. Contrary, ibuprofen dissolved in the presence of fruit juice was significantly lower. Differences in the dissolution profiles of investigated preparations suggest that their interchangeability should be additionally considered and demonstrated with in vivo bioequivalence studies. Presence of different substances in the medium can affect dissolution properties of ibuprofen, emphasizing the importance of the patient's compliance.
Subject(s)
Ibuprofen/analysis , Interchange of Drugs , Dissolution , Tablets , In Vitro Techniques/methods , Pharmaceutical Preparations/analysis , Drug Liberation/drug effectsABSTRACT
Abstract Candidiasis is one of the most common fungal infections of oral cavity in humans, causing great oral discomfort, pain and aversion to food. To develop more effective antifungal systems for the treatment of oral candidiasis, an oral mucoadhesive wafer containing sertaconazole solid dispersion (STZ-SD) was developed in this study. Dispersion of STZ in Soluplus® as a solubility enhancement excipient was done by melting, solvent evaporation and freeze drying method at various STZ to Soluplus® ratios. The optimized STZ-SD was then incorporated in the sodium carboxymethyl cellulose (SCMC) gel, xanthan gum gel, or their combination to prepare the lyophilized wafers. The swelling capacity, porosity, and mechanical, release and mucoadhesive properties of the wafers, together with their antifungal activity, were then evaluated. The melting method sample with the ratio of 8:1 showed the best results in terms of saturation solubility and dissolution rate. The STZ-SD-composite wafer exhibited higher hardness and mucoadhesion, as compared to those made of the SCMC polymer. The STZ-SD-wafer also exhibited a greater antifungal effect when compared to the STZ-wafer. The present study, thus, suggested that the STZ-SD-wafer could serve as a novel effective delivery system for oral candidiasis treatment.
Subject(s)
Mouth/pathology , Candidiasis, Oral/drug therapy , Food/classification , Freeze Drying/classification , Gingiva/abnormalitiesABSTRACT
Objetivo: incorporar la indometacina en sistemas autoemulsionables de liberación con la finalidad de aumentar su solubilidad en medio acuoso, la velocidad de disolución y permeación in vitro. Metodología: se llevaron a cabo ensayos de solubilidad al equilibrio para preparar formulaciones con los excipientes, en los cuales la indome-tacina presentó mayor incremento de solubilidad; los sistemas fueron caracterizados por medio del tiempo de autoemulsificación, estabilidad física, tamaño de partícula, potencial zeta, perfiles de disolución y permeación a través de membrana sintética. Resultados: el diseño experimental de los sistemas autoemulsionables de liberación permitió crear formulaciones que aumentaron la solubilidad de la indometacina en un orden de 105 veces con respecto a la solubilidad acuosa. Las formulaciones que resultaron viables presentaron tiempos de autoemulsificación menores que 60 segundos, además, las distribuciones de tamaño de partícula de las dispersiones fueron inferiores a los 300 nm, presentó índices de polidispersión inferiores a 0,3 y valores de potencial zeta menores de -25 mV. Los perfiles de disolución mostraron que las formulaciones cumplen con un valor de factor de similitud mayor que 50, además, la permeabilidad a través de membrana sintética es mayor para las formulaciones autoemulsionables que el producto de referencia. Conclusiones: la formulación de indometacina en sistemas autoemulsionables de liberación incrementa la solubilidad en medio acuoso, aumenta la disolución y liberación. Estos resultados sugieren que la administración oral de indometacina incorporada en sistemas autoe-mulsionables puede acelerar el inicio del efecto farmacológico.
SUMMARY Aim: To load indomethacin into self-emulsifying delivery systems in order to increase, water-solubility, rate dissolution and in vitro permeation. Methodology: Equilibrium solubility tests were carried out to prepare formulations with the excipients, in which indomethacin presented a greater increase in solubility; the systems were characterized by self-emulsification time, physical stability, particle size, zeta potential, dissolution profiles and permeation through synthetic membrane. Results: The experimental design of self-emulsifying delivery systems allowed to create formulations that increase the solubility of indomethacin in an order of 105 times with respect to the aqueous solubility. The feasible formulations presented autoemulsification times less than 60 seconds, in addition, the particle size distributions of the dispersions were less than 300 nm, with polydispersity index smaller than 0.3, and zeta potential values lower than -25 mV. The dissolution profiles showed that the formulations comply with a similarity factor value greater than 50, in addition, the permeability through a synthetic membrane is higher for the self-emulsifying formulations than the reference product. Conclusion: The formulation of indomethacin into self-emulsifying delivery systems enhances the solubility in aqueous medium, increases dissolution and accelerate release. These results suggest that the oral administration of indomethacin incorporated into self-emulsifying delivery systems can accelerate the onset of the pharmacological effect.
Objetivo: incorporar a indometacina em sistemas de liberação autoemulsificantes a fim de aumentar sua solubilidade em meio aquoso, a taxa de dissolução e permeação in vitro. Metodologia: foram realizados testes de solubilidade de equilíbrio para preparar formulações com os excipientes, nas quais a indometacina apresentou maior aumento na solubilidade; os sistemas foram caracterizados quanto ao tempo de autoemulsificação, estabilidade física, tamanho de partícula, potencial zeta, perfis de dissolução e permeação através de membrana sintética. Resultados: o desenho experimental dos sistemas de liberação autoemulsificantes permitiu a criação de formulações que aumentaram a solubilidade da indometacina na ordem de 105 vezes em relação à solubilidade aquosa. As formulações que se mostraram viáveis apresentaram tempos de autoemulsificação inferiores a 60 segundos, além disso, as distribuições granulométricas das dispersões foram inferiores a 300 nm, apresentaram índices de polidispersidade inferiores a 0,3 e valores de potencial zeta inferiores a -25 mV. Os perfis de dissolução mostraram que as formulações atendem a um valor de fator de similaridade maior que 50, além disso, a permeabilidade através da membrana sintética é maior para as formulações autoemulsionantes do que para o produto de referência. Conclusões: a formulação de indometacina em sistemas de liberação autoemulsificantes aumenta a solubilidade em meio aquoso, aumenta a dissolução e a liberação. Esses resultados sugerem que a administração oral de indometacina incorporada em sistemas autoemulsificantes pode acelerar o início do efeito farmacológico.
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The purpose of this work was to elaborate a diagnosis of the dissolution test in Africa in comparison with Brazil, evaluating the dissolution profile of low solubility drugs such as albendazole, ibuprofen, furosemide, glibenclamide, hydrochlorothiazide and carvedilol to ascertain their quality. The dissolution profiles were evaluated by utilizing the United States Pharmacopeia (USP). The glibenclamide medicine was evaluated according to the Food and Drug Administration (FDA), while a dissolution method was developed for the carvedilol medicine. A filter selection test for all the drugs showed that cannula is suitable for all, except for carvedilol, which is centrifuged. The various brands of Nigerian and Brazilian medicines tested showed some statistical differences. The suitable conditions that allowed the dissolution of carvedilol to be determined were the USP type II apparatus at 75 rpm containing 900 mL of acetate buffer, pH 4.5. The results of the dissolution test showed that out of the 17 different brands of Brazilian medicines and 17 different products from Nigeria, 94.12% and 58.82% passed respectively
O objetivo deste trabalho foi elaborar um diagnóstico do teste de dissolução na África em comparação ao Brasil, avaliando o perfil de dissolução de medicamentos de baixa solubilidade como albendazol, ibuprofeno, furosemida, glibenclamida, hidroclorotiazida e carvedilol para verificar sua qualidade.Os perfis de dissolução foram avaliados utilizando a Farmacopeia dos Estados Unidos (USP). O medicamento glibenclamida foi avaliado de acordo com a Food and Drug Administration (FDA), enquanto um método de dissolução foi desenvolvido para o medicamento carvedilol.Um teste de seleção de filtro para todos os medicamentos mostrou que a cânula é adequada para todos, exceto para o carvedilol, que é centrifugado. As diversas marcas de medicamentos Nigerianos e Brasileiros testadas apresentaram algumas diferenças estatísticas. As condições adequadas que permitiram a determinação da dissolução do carvedilol foram o aparelho USP tipo II a 75 rpm contendo 900 mL de tampão acetato, pH 4,5. Os resultados do teste de dissolução mostraram que das 17 diferentes marcas de medicamentos brasileiros e 17 diferentes produtos da Nigéria, 94,12% e 58,82% foram aprovados, respectivamente
Subject(s)
Solubility , Brazil/ethnology , Pharmaceutical Preparations/analysis , Africa/ethnology , Dissolution , United States Food and Drug Administration , Albendazole/pharmacology , Ibuprofen , Carvedilol/pharmacology , Furosemide/pharmacology , Methods , Acetates/adverse effectsABSTRACT
The amorphous solid dispersion is one of the most effective formulation approaches to enhance the oral bioavailability of poorly water-soluble drugs. However, the amorphous drugs tend to crystallize during storage or dissolution due to inadequate formulations, preparation techniques, storage and dissolution conditions, thus negating their advantages. Meanwhile, it is often difficult to establish in vitro-in vivo correlation for amorphous solid dispersions owing to the difference between dissolution media and physiological environments and between the apparent concentration and membrane transport flux, the dynamic process of the in vivo absorption, which put great challenges to the development of amorphous solid dispersion products. This review covers the recent progress on the mechanistic study of the in vitro dissolution and in vivo absorption of amorphous solid dispersions, aiming to provide guidance for the formulation development of poorly soluble drugs.
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The present study explored the effect of co-amorphous technology in improving the dissolution rate and stability of silybin based on the puerarin-silybin co-amorphous system prepared by the spray-drying method. Solid-state characterization was carried out by powder X-ray diffraction(PXRD), polarizing microscopy(PLM), Fourier transform infrared spectroscopy(FT-IR), differential scanning calorimetry(DSC), etc. Saturated powder dissolution, intrinsic dissolution rate, moisture absorption, and stability were further investigated. The results showed that puerarin and silybin formed a co-amorphous system at a single glass transition temperature which was higher than that of any crude drug. The intrinsic dissolution rate and supersaturated powder dissolution of silybin in the co-amorphous system were higher than those of the crude drug and amorphous system. The co-amorphous system kept stable for as long as three months under the condition of 40 ℃, 75% relative humidity, which was longer than that of the single amorphous silybin. Therefore, the co-amorphous technology could significantly improve the dissolution and stability of silybin.
Subject(s)
Calorimetry, Differential Scanning , Desiccation , Drug Compounding/methods , Drug Stability , Silymarin , Solubility , Spectroscopy, Fourier Transform Infrared , Technology , X-Ray DiffractionABSTRACT
Objective:To establish methods for HPLC fingerprints and simultaneous determination of multi-index components before and after compatibility of Salvia miltiorrhiza and Angelica sinensis, so as to analyze the dissolution rate of the main compounds. Methods:The extracts of Salvia miltiorrhiza, Angelica sinensis and their compatibility were prepared. The separation was performed on an Eclipse XDB-C18 column (4.6 mm×250 mm,5 μm), mobile phase with 0.1% phosphoric acid aqueous solution-acetonitrile for gradient elution, flow rate at 1.0 ml/min, column temperature was maintained at 35 ℃, and the detection wavelength was set at 280 nm. The HPLC fingerprint were established before and after the compatibility of Salvia miltiorrhiza and Angelica sinensis, and the shared patterns of the fingerprint were obtained to gain chromatographic peaks. The content of 9 components Danshensu, caffeic acid, rosmarinic acid, salvianolic acid B, salvianolic acid A, tanshinone Ⅱ A, ferulic acid, chlorogenic acid and Yangchuanxiong lactone were determinated, and the changes of dissolution rate of each compound before and after the compatibility were analyzed. Results:The determination method for the multi- components with HPLC is precise and the components (waiting to be determinate) in the solution were stable within 48 hours, and the RSD values of each chromatographic peak were <5.0%. The nine components showed good linear relationships within their own ranges, and the recovery rate was in compliance with regulations. The fingerprint similarities of each sample were ?0.9. After the compatibility of Salvia miltiorrhiza and Angelica sinensis, a total of seventeen common peaks were calibrated, ten of which were from Salvia miltiorrhiza, seven from Angelica sinensis. No new components was found under this chromatographic condition. After the combination of these two material medicica decoction, the average dissolution rates of rosmarinic acid, salvianolic acids and Danshensu in Salvia miltiorrhiza were significantly lower than those of the single decoction group ( P<0.05 or P<0.01); the average dissolution rates of caffeic acid in Salvia miltiorrhiza was significantly higher than that of the single decoction group ( P<0.01); the average dissolution rates of chlorogenic acid and ferulic acid in Angelica sinensis were significantly higher than that of the single decoction group ( P<0.05 or P<0.01); the average dissolution rate of Yangchuanxiong lactone after the compatibility was not statistically different than that of single decoction group. Conclusion:The characteristic peaks of HPLC fingerprint of the compatibility of Salvia miltiorrhiza and Angelica sinensis did not increase under this chromatographic condition, which had a significant effect on the dissolution of index components.
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Objective:To study the efficacy and influencing factors of ursodeoxycholic acid (UDCA) in the treatment of cholesterol gallstone, so as to provide reference for the treatment of cholesterol gallstone by internal medicine.Methods:From March 1, 2017 to March 31, 2018, at outpatient department of gastroenterology of 9 Beijing medical centers including Peking University People′s Hospital, the Sixth Medical Center of PLA General Hospital, Beijing Huaxin Hospital, PLA Rocket Force Characteristic Medical Center, Peking University Aerospace Center Hospital, Beijing Youan Hospital of Capital Medical University and Beijing Tiantan Hospital of Capital Medical University, Beijing Tongren Hospital of Capital Medical University, and Beijing Shijitan Hospital of Capital Medical University, the data of patients with cholesterol gallstone treated by UDCA were collected. The inclusion criteria were that the largest diameter of stone was ≤10 mm and the stone was not detected under X-ray. The treatment plan was taking UDCA orally for 6 months at a dose of 10 mg·kg -1·d -1. The basic information of patients, the ultrasound examination results before treatment and 6 months after treatment, and scores of biliary abdominal pain and dyspepsia symptom were collected. Univariate and multivariate logistic regression were used to analyze the influencing factors of the efficacy in gallstrone dissolution by UDCA, and Wilcoxon signed rank test was used for statistical analysis. Results:A total of 215 patients were enrolled. The complete dissolution rate of gallstone was 19.5% (42/215) and partial dissolution rate was 50.7% (109/215), and the total effective rate was 70.2% (151/215). The complete dissolution rate of sandy stone was significantly higher than that of lumped stones (37.0%(17/46) vs. 14.8%(25/169); OR=3.377, 95% confidence interval (95% CI) 1.621 to 7.035, P=0.001). In lumped stones, the complete dissolution rate of the stones with diameter ≤5 mm was significantly higher than that of the stones with diameter >5 mm (37.5%(9/24) vs. 11.0%(16/145); OR=4.837, 95% CI 1.823 to 12.839, P=0.002). The complete dissolution rate of patients with higher body mass index ( OR=0.872, 95% CI 0.764 to 0.995, P=0.043) and longer disease course ( OR=0.942, 95% CI 0.912 to 0.973, P<0.001) was low. The results of multivariate logistic analysis indicated that long disease course of gallstone ( OR=0.940, 95% CI 0.908 to 0.974, P=0.001), rough gallbladder wall ( OR=0.438, 95% CI 0.200 to 0.962, P=0.040) and lumped stone ( OR=0.236, 95% CI 0.101 to 0.550, P=0.001) were independent risk factors of influencing the efficacy of stone dissolution by UDCA. As for lumped stones, the independent risk factors included long disease course of gallstone ( OR=0.926, 95% CI 0.877 to 0.978, P=0.006) and stone diameter >5 mm ( OR=0.142, 95% CI 0.043 to 0.470, P=0.001). After 6 months of UDCA treatment, score of biliary abdominal pain decreased from 0 (0 to 6) to 0 (0 to 0) and the score of dyspepsia symptom decreased from 1 (0 to 2) to 0 (0 to 0), and the differences between before treatment and after treatment were statistically significant ( Z=-8.50, and -9.13, both P<0.001). Conclusions:UDCA has a certain efficacy in cholesterol gallstone dissolution and can ease biliary abdominal pain and dyspepsia symptom. Long disease course of gallstone, rough gallbladder wall and stone diameter >5 mm are independent risk factors of poor efficacy in gallstone dissolution by UDCA.
ABSTRACT
Abstract In the work the andrographolide (AG)-solid dispersions (SDs) were prepared by the spray-drying method, using polyethylene glycol 8000 (PEG8000), Poloxamer188, polyvinylpyrrolidone K30 (PVPK30), Soluplus® as carrier materials. The effect of different polymers as carrier materials on the properties of the AG-SDs were studied. The results showed obvious differences in intermolecular interaction, thermal stability, drug state, powder properties, dissolution behavior, and so on of AG-SDs prepared using different polymers as carrier materials. AG-PEG8000-SD was a partial-crystalline and partial-amorphous powder with smaller surface area and pore volume, but it was easy to wetting and did not swell in contact with dissolved medium. AG-Soluplus®-SD was completely amorphous powder with larger specific surface area and pore volume, but it swelled in contact with water. Therefore, the dissolution profile of AG in AG-PEG8000-SD was similar to that in AG-Soluplus®-SD. Soluplus® and PEG8000 were suitable polymers to design AG-SDs, considering both physicochemical properties and dissolution behaviors. The results of this reseach showed that when selecting carrier materials for SD, we should not only consider the state of drugs in SD and the powder properties of SD, but also consider whether there is swelling when the carrier materials are in contact with the dissolution medium.
Subject(s)
Polyethylene Glycols/adverse effects , Dissolution , Methods , Polymers/analysis , Pharmaceutical Preparations/analysis , Water , Spray DryingABSTRACT
For a drug to excerpt pharmacological action after oral intake, it first needs to be released from the formulation, get into solution (dissolve), be absorbed, and reach the systemic circulation. Since only solubilized drugs can be absorbed, and thus have therapeutic effect, the understanding of the dissolution and drug release processes of a drug product is of primary importance. Such understanding allows a robust formulation development with an ideal in vivo performance. In order to meet set standards, the performance assessment of oral drug products, such as dissolution testing, often applies conditions that are not reflective of the in vivo environment. The use of non-physiologically relevant dissolution method during the drug product development phase can be misleading and give poor mechanistic understanding of the in vivo dissolution process. Hence, we hypothesized that applying physiologically relevant conditions to the dissolution test would result in more accurate in vivo predictability for a robust and precise development process. Since the buffering system in the intestinal lumen operates at low molarity values, phosphate buffer at low buffer capacity was used as a first approach to an in vivo relevant parameter. Furthermore, a biphasic system was used, that is, the low buffer capacity medium was paired with an organic layer (n-octanol) to mimic the concurrent drug absorption that happens with the in vivo dissolution. Both poorly and highly soluble drugs in immediate release formulations (ibuprofen and metronidazole, respectively) were tested in this set-up to assess the dissolution in the aqueous medium and the partitioning to the organic phase. Additionally, enteric coated formulations were tested in bicarbonate buffer at the in vivo reported molarities values to assess the impact of buffer species on drug dissolution. The evaluated parameters were the buffer system (bicarbonate buffer vs. phosphate buffer), buffer capacity and medium pH. In all approaches, dissolution was also carried out in compendial buffer for comparison purposes. Our results demonstrate that the USP-recommended dissolution method greatly lacked discriminatory power, whereas low buffer capacity media discriminated between manufacturing methods. The use of an absorptive phase in the biphasic dissolution test assisted in controlling the medium pH due to the drug removal from the aqueous medium. Hence, the applied noncompendial methods were more discriminative to drug formulation differences and manufacturing methods than conventional dissolution conditions. In this study, it was demonstrated how biphasic dissolution and a low buffer capacity can be used to assess drug product performance differences. This can be a valuable approach during the early stages of drug product development for investigating drug release with improved physiological relevance. Similarly, all the enteric coated formulations displayed a fast release in phosphate buffer and complied with the compendial performance specifications. On the other hand, they all had a much slower drug release in bicarbonate buffer and failed the USP acceptance criteria. Also, the nature of the drug (acid vs base) impacted the dissolution behavior in bicarbonate buffer. This study indicates that compendial dissolution test for enteric coated tablets lacks physiological relevance and it needs to be reevaluated. Thus, an in vivo relevant performance method for EC products is needed. Overall, the findings of this thesis comprehensively demonstrates that meaningful differences in performance and accordance to clinical reports were only obtained when physiological relevant conditions were applied. Hence, our results indicate that the central hypothesis was answered positively
Para que um medicamento exerça a ação farmacológica após a ingestão oral, ele primeiro precisa ser liberado da formulação, dissolver, ser absorvido e atingir a circulação sistêmica. Uma vez que apenas medicamentos solubilizados podem ser absorvidos e, assim, ter efeito terapêutico, a compreensão dos processos de dissolução e liberação de um medicamento é de extrema importância. Tal compreensão permite o desenvolvimento de uma formulação robusta com o desempenho in vivo ideal. Para atender aos padrões regulatórios previamente estabelecidos, a avaliação da performance de formulações orais, como por exemplo, o teste de dissolução, frequentemente aplica condições que não refletem o ambiente fisiológico. O uso de métodos de dissolução não fisiologicamente relevante durante a fase de desenvolvimento do medicamento pode gerar resultados equivocados sem uma compreensão mecanistica do processo de dissolução in vivo. Portanto, a hipótese desse trabalho é que a aplicação de condições fisiologicamente relevantes no teste de dissolução resultaria em uma predição mais precisa da dissolução in vivo para um processo de desenvolvimento robusto e preciso. Uma vez que o sistema tampão no lúmen intestinal possui baixa molaridade, o tampão fosfato com baixa capacidade tamponante foi usado como uma primeira abordagem como um meio de dissolução fisiologicamente relevante. Além disso, foi utilizado um sistema bifásico, ou seja, o meio de baixa capacidade tamponante combinado a uma fase orgânica (n-octanol) para imitar a absorção in vivo. Formulações de liberação imediata contendo fármacos de baixa e de alta solubilidade (ibuprofeno e metronidazol, respectivamente) foram testadas no sistema bifásico para avaliar a dissolução no meio aquoso e a partição para a fase orgânica. Ademais, formulações com revestimento entérico foram testadas em tampão bicarbonato nos valores de molaridades fisiológicos para avaliar o impacto da espécie tamponante na dissolução do fármaco. Os parâmetros avaliados foram o sistema tampão (tampão bicarbonato vs. tampão fosfato), capacidade tamponante e pH médio. Em todas as abordagens, a dissolução também foi realizada em tampão farmacopeico para fins de comparação. Nossos resultados demonstraram que o método de dissolução farmacopeico não foi discriminativo, enquanto o meio com menor capacidade tamponante diferenciou entre as formulações obtidas via granulação úmida ou compressão direta. Ademais, a utilização da fase orgânica no teste de dissolução bifásica auxiliou no controle do pH do meio aquoso. Portanto, os métodos não compendiais aplicados foram mais discriminativos do que as condições de dissolução convencionais. Neste estudo, foi demonstrado como a dissolução bifásica e uma baixa capacidade tamponante podem ser usadas para avaliar as diferenças na performance de formulações. Esta pode ser uma abordagem valiosa durante os estágios iniciais do desenvolvimento de medicamentos para investigar a liberação destes sob condições fisiologicamente relevantes. Da mesma forma, todas as formulações com revestimento entérico exibiram uma liberação rápida em tampão de fosfato e atenderam às especificações farmacopeicas. Entretanto, a liberação do fármaco foi muito mais lenta em tampão de bicarbonato e consequentemente não cumpriram com as especificações farmacopeicas. Além disso, a natureza do fármaco (ácido vs. base) impactou o comportamento de dissolução no tampão de bicarbonato. Este estudo indica que o teste de dissolução convencional para comprimidos de liberação retardada não possui relevância fisiológica e precisa ser reavaliado. Portanto, os resultados desta tese demonstram de forma abrangente que diferenças significativas na performance condizentes com relatórios clínicos foram obtidas apenas quando as condições fisiológicas relevantes foram aplicadas. Esses resultados indicam que a hipótese central foi respondida positivamente