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1.
Electron. j. biotechnol ; 52: 21-29, July. 2021. ilus, tab, graf
Article in English | LILACS | ID: biblio-1283484

ABSTRACT

BACKGROUND: Super-paramagnetic iron oxide nanoparticles (SPION) contain a chemotherapeutic drug and are regarded as a promising technique for improving targeted delivery into cancer cells. RESULTS: In this study, the fabrication of 5-fluorouracil (5-FU) was investigated with loaded Dextran (DEXSPION) using the co-precipitation technique and conjugated by folate (FA). These nanoparticles (NPs) were employed as carriers and anticancer compounds against liver cancer cells in vitro. Structural, magnetic, morphological characterization, size, and drug loading activities of the obtained FA-DEX-5-FUSPION NPs were checked using FTIR, VSM, FESEM, TEM, DLS, and zeta potential techniques. The cellular toxicity effect of FA-DEX-5-FU-SPION NPs was evaluated using the MTT test on liver cancer (SNU-423) and healthy cells (LO2). Furthermore, the apoptosis measurement and the expression levels of NF-1, Her-2/neu, c-Raf-1, and Wnt-1 genes were evaluated post-treatment using flow cytometry and RT-PCR, respectively. The obtained NPs were spherical with a suitable dispersity without noticeable aggregation. The size of the NPs, polydispersity, and zeta were 74 ± 13 nm, 0.080 and 45 mV, respectively. The results of the encapsulation efficiency of the nano-compound showed highly colloidal stability and proper drug maintenance. The results indicated that FA-DEX-5-FU-SPION demonstrated a sustained release profile of 5-FU in both phosphate and citrate buffer solutions separately, with higher cytotoxicity against SNU-423 cells than against other cells types. These findings suggest that FA-DEX-SPION NPs exert synergistic effects for targeting intracellular delivery of 5-FU, apoptosis induction, and gene expression stimulation. CONCLUSIONS: The findings proved that FA-DEX-5-FU-SPION presented remarkable antitumor properties; no adverse subsequences were revealed against normal cells.


Subject(s)
Humans , Carcinoma, Hepatocellular/drug therapy , Fluorouracil/administration & dosage , Liver Neoplasms/drug therapy , Polymers , Gene Expression/drug effects , Drug Delivery Systems , Apoptosis/drug effects , Reverse Transcriptase Polymerase Chain Reaction , Delayed-Action Preparations , Nanoparticles/administration & dosage , Magnetite Nanoparticles , Flow Cytometry
2.
Article in Chinese | WPRIM | ID: wpr-921635

ABSTRACT

In this paper, co-processed lactose SuperTab 40 LL was selected as fillers to study the preparation of musk sustained-release mini-tablets in the Xihuang multiple-unit drug release system. Musk sustained-release tablets containing different proportions of SuperTab 40 LL and MCC were prepared under various pressures, and then the compressibility and compactibility of these prescriptions were evaluated by Walker, Heckel and Ryshkewitch-Duckworth equations. In addition, the fluidity of the prescriptions was evaluated by parameters of Kawakita equation. There was a comprehensive analysis of the effect of SuperTab 40 LL on musk sustained-release mini-tablets combined with the appearance of SuperTab 40 LL and their tensile strength. The results shown that SuperTab 40 LL had better compression process through the Heckel equation, and the direct compression process of drug powders with excipients can be analyzed by the Kawakita and Ryshkewitch-Duckworth equations. As a new type of co-processed lactose, SuperTab 40 LL had a good fluidity and compactibility. SuperTab 40 LL may undergo particle crushing and plastic deformation during the compression process, which increased the contact area and bonding sites between the particles, and aggregated and shaped the mixed powder easy. Moreover, MCC showed a synergistic effect, and the combined application with SuperTab 40 ll could effectively improve the fluidity and compressibility of the musk sustained-release powder. When the ratio of SuperTab 40 LL and MCC was 2∶1, musk sustained-release mini-tablets had a high drug loading capacity and good compactibility in line with the design objectives.


Subject(s)
Delayed-Action Preparations , Drug Compounding , Excipients , Fatty Acids, Monounsaturated , Models, Theoretical , Powders , Tablets
3.
Clinics ; 76: e1907, 2021. tab, graf
Article in English | LILACS | ID: biblio-1153930

ABSTRACT

OBJECTIVES: This study was designed to evaluate the clinical efficacy of controlled-release morphine tablets combined with celecoxib in relieving osteocarcinoma-related pain and the effects of the combination on WNK1 expression. METHODS: A total of 110 patients with osteocarcinoma-related pain were selected and divided into two groups based on the treatment administered, including the control group (treated with controlled-release morphine tablets alone) and the study group (treated with a combination of controlled-release morphine tablets and celecoxib). We compared the treatment efficacy, pain level (visual analog scale (VAS)), time of onset of breakthrough pain (BTP), dose of morphine, incidence of adverse events, quality of life (QOL) score, and With-no-lysine 1 (WNK1) expression in the peripheral blood (PB) as determined with qRT-PCR before and after treatment, of the two groups. RESULTS: The total effective rate of the study group was higher than that of the control group, while the VAS score, time of onset of BTP, dose of morphine, incidence of adverse events, QOL score, and relative WNK1 expression in the PB were lower than those of the control group (p<0.05). CONCLUSION: Combination treatment with controlled-release morphine tablets and celecoxib can be extensively used in the clinical setting because it effectively improves the symptoms, QOL score, and adverse effects in patients with osteocarcinoma-related pain.


Subject(s)
Humans , Quality of Life , Morphine , Treatment Outcome , Delayed-Action Preparations , Computers, Handheld , Pain Management , Celecoxib , WNK Lysine-Deficient Protein Kinase 1 , Analgesics, Opioid/therapeutic use
4.
Rev. chil. pediatr ; 91(2): 251-254, abr. 2020. graf
Article in Spanish | LILACS | ID: biblio-1098899

ABSTRACT

Resumen: Introducción: La hemorragia digestiva por hipertensión portal, sin alternativa de tratamiento endos- cópico o quirúrgico por localizaciones ectópicas, no identificadas del sitio de sangrado o caracterís ticas anatómicas, constituye un desafío terapéutico en Pediatría. El tratamiento habitual incluye la infusión de octreótido endovenoso. En los últimos años, la presentación de octreótido de liberación prolongada (OCT-LAR) para administración mensual intramuscular, resulta una alternativa tera péutica atractiva. Objetivo: Reportar el caso de un lactante con hemorragia digestiva por hiperten sión portal que recibió tratamiento exitoso con OCT-LAR. Caso Clínico: Paciente de 8 meses de vida, con malformación de vena porta extrahepática y episodios reiterados de sangrados digestivos con re querimientos transfusionales e infusiones de octréotido, sin posibilidad de tratamiento endoscópico o quirúrgico. Indicamos OCT-LAR intramuscular mensualmente. Después de diez meses de iniciado el tratamiento, el paciente no repitió sangrados digestivos y no presentó efectos adversos relacionados a la medicación. Conclusión: Consideramos que el reporte de este caso puede resultar de utilidad al presentar una nueva alternativa para el tratamiento de pacientes pediátricos con sangrado digestivo por hipertensión portal sin posibilidades terapéuticas convencionales.


Abstract: Introduction: Upper gastrointestinal bleeding (UGIB) secondary to portal hypertension (PHT), without endoscopic or surgical treatment options due to an ectopic or unidentified bleeding site or the patient's anatomic characteristics, is challenging in pediatric hepatology. The usual treatment in these cases includes intravenous Octreotide. Recently, the availability of long-acting release Octreo tide (OCT-LAR) for monthly intramuscular administration has become an interesting therapeutic alternative. Objective: To report the case of an infant with UGIB due to PHT who was successfully treated with OCT-LAR. Clinical Case: Eight-month-old patient with repeated episodes of UGIB due to extrahepatic portal vein malformation, requiring blood transfusions, and intravenous octreotide infusions. As neither endoscopic nor surgical treatment were feasible, we decided to start IM OCT- LAR monthly. After ten months of treatment, the patient did not present bleeding episodes. No medication-related events were observed. Conclusion: We consider that this report could help in the management of similar pediatric patients with UGIB due to PHT without conventional therapeutic possibilities.


Subject(s)
Humans , Male , Infant , Gastrointestinal Agents/administration & dosage , Octreotide/administration & dosage , Duodenal Diseases/drug therapy , Gastrointestinal Hemorrhage/drug therapy , Hypertension, Portal/complications , Gastrointestinal Agents/therapeutic use , Octreotide/therapeutic use , Delayed-Action Preparations , Duodenal Diseases/etiology , Gastrointestinal Hemorrhage/etiology , Injections, Intramuscular
5.
Article in Chinese | WPRIM | ID: wpr-828940

ABSTRACT

OBJECTIVE@#To study the plasma concentration and pharmacokinetics of 3, 29-Dibenzoyl Karounitriol (3, 29-DK) from sustained- release pellets and extracts of Trichosanthes at different time points in rats using high-performance liquid chromatography- tandem mass spectrometry (LC-MS/MS).@*METHODS@#Healthy male SD rats were given a single gavage of Trichosanthes sustained-release pellets or Trichosanthes extract, and orbital blood samples were taken at different time points within 48 h after drug administration in the pellet group and within 5 h in Trichosanthes extract group for determination of the plasma concentrations of 3, 29-DK using LC-MS/MS. The standard curve of 3, 29-DK content was established, and the specificity, minimum detection limit, precision and accuracy, extraction recovery, stability and matrix effect of LC-MS/MS analysis were assessed. The mean plasms levels of 3, 29-DK at different time points after the drug administration were determined and its pharmacokinetic parameters were calculated using Das 2.0 software.@*RESULTS@#LC-MS/MS analysis showed a good linearity of 3, 29-DK concentration within the range of 0.5-32 ng/mL, and the results of methodological validation confirmed the validity of this method for biological sample determination. Trichosanthes sustained-release pellets and Trichosanthes extract showed significant differences in their AUC, AUC, MRT, MRT, t and T of 3, 29-DK after administration in rats ( < 0.05).@*CONCLUSIONS@#Trichosanthes sustained-release pellets are capable of sustained-release of 3, 29-DK in rats, and thus provides a basis for the study of new dosage forms of Trichosanthes.


Subject(s)
Animals , Chromatography, High Pressure Liquid , Delayed-Action Preparations , Male , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Tandem Mass Spectrometry , Trichosanthes
6.
Article in Chinese | WPRIM | ID: wpr-828521

ABSTRACT

OBJECTIVE@#To study the plasma concentration and pharmacokinetics of 3, 29-Dibenzoyl Karounitriol (3, 29-DK) from sustained- release pellets and extracts of Trichosanthes at different time points in rats using high-performance liquid chromatography- tandem mass spectrometry (LC-MS/MS).@*METHODS@#Healthy male SD rats were given a single gavage of Trichosanthes sustained-release pellets or Trichosanthes extract, and orbital blood samples were taken at different time points within 48 h after drug administration in the pellet group and within 5 h in Trichosanthes extract group for determination of the plasma concentrations of 3, 29-DK using LC-MS/MS. The standard curve of 3, 29-DK content was established, and the specificity, minimum detection limit, precision and accuracy, extraction recovery, stability and matrix effect of LC-MS/MS analysis were assessed. The mean plasms levels of 3, 29-DK at different time points after the drug administration were determined and its pharmacokinetic parameters were calculated using Das 2.0 software.@*RESULTS@#LC-MS/MS analysis showed a good linearity of 3, 29-DK concentration within the range of 0.5-32 ng/mL, and the results of methodological validation confirmed the validity of this method for biological sample determination. Trichosanthes sustained-release pellets and Trichosanthes extract showed significant differences in their AUC, AUC, MRT, MRT, t and T of 3, 29-DK after administration in rats ( < 0.05).@*CONCLUSIONS@#Trichosanthes sustained-release pellets are capable of sustained-release of 3, 29-DK in rats, and thus provides a basis for the study of new dosage forms of Trichosanthes.


Subject(s)
Animals , Area Under Curve , Benzoates , Pharmacokinetics , Chromatography, Liquid , Delayed-Action Preparations , Male , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Tandem Mass Spectrometry , Trichosanthes , Chemistry
7.
Bol. latinoam. Caribe plantas med. aromát ; 19(4): 344-356, 2020. tab, ilus
Article in English | LILACS | ID: biblio-1283652

ABSTRACT

Many chronic diseases require repetitive injections as maintenance treatment. It is therefore important to investigate a possible alternative. A simulated subcutaneous implant prototype was fabricated as a polymer matrix covered by cylinder-shape tubing having a porous membrane. Sucrose, bovine serum albumin, and gelatin were selected as matrix excipients. Eight APIs with different physiochemical properties were used to investigate the releasing mechanism. Drug release was tested through an in vitrodissolution apparatus. Drug release of eight APIs followed zero-order kinetics with a minimum 12-hour duration. Release rates also showed linear correlations with the APIs' solubilities under physiological pH. For releasing mechanism studies, different combinations of matrix and membrane were investigated in detail. A 144-hour continuous zero-order release of caffeine was achieved as the best controlled simulated prototype. The results showed that drug release of our simulated prototype was primarily achieved by drug diffusion rather than dissolution.


Muchas enfermedades crónicas requieren inyecciones repetitivas como tratamiento de mantenimiento. Por lo tanto, es importante investigar una posible alternativa. Se fabricó un prototipo de implante subcutáneo simulado a partir de una matriz de polímero cubierta por un tubo en forma de cilindro que tiene una membrana porosa. La sacarosa, la albúmina de suero bovino y la gelatina se seleccionaron como excipientes matriciales. Se utilizaron ocho APIs con diferentes propiedades fisicoquímicas para investigar el mecanismo de liberación. La liberación del fármaco se probó a través de un aparato de disolución in vitro. La liberación del fármaco de las ocho APIs siguió una cinética de orden cero con una duración mínima de 12 horas. Las tasas de liberación también mostraron correlaciones lineales con las solubilidades de las APIs a pH fisiológico. Para los estudios de mecanismos de liberación, se investigaron en detalle diferentes combinaciones de matriz y membrana. El prototipo simulado con mejor control logró una liberación continua de cafeína de orden cero durante 144 horas. Los resultados mostraron que la liberación del fármaco del prototipo simulado ocurrió principalmente mediante la difusión del fármaco en lugar de la disolución.


Subject(s)
Pharmaceutical Preparations/administration & dosage , Drug Implants/metabolism , In Vitro Techniques , Pilot Projects , Simulation Technique , Chromatography, High Pressure Liquid , Subcutaneous Tissue , Delayed-Action Preparations , Drug Evaluation, Preclinical , Drug Liberation , Freeze Drying
8.
Arch. endocrinol. metab. (Online) ; 63(6): 601-607, Nov.-Dec. 2019. tab
Article in English | LILACS | ID: biblio-1055017

ABSTRACT

ABSTRACT Growth hormone therapy with daily injections of recombinant human growth hormone has been available since 1985, and is shown to be safe and effective treatment for short stature in children and for adult growth hormone deficiency. In an effort to produce a product that would improve patient adherence, there has been a strong effort from industry to create a long acting form of growth hormone to ease the burden of use. Technologies used to increase half-life include depot formulations, PEGylated formulations, pro-drug formulations, non-covalent albumin binding growth hormone and growth hormone fusion proteins. At present, two long acting formulations are on the market in China and South Korea, and several more promising agents are under clinical investigation at various stages of development throughout the world. Arch Endocrinol Metab. 2019;63(6):601-7


Subject(s)
Humans , Child , Adult , Human Growth Hormone/administration & dosage , Growth Disorders/drug therapy , Drug Administration Schedule , Drug Design , Chemistry, Pharmaceutical , Human Growth Hormone/pharmacokinetics , Human Growth Hormone/chemistry , Delayed-Action Preparations
9.
Article in Chinese | WPRIM | ID: wpr-775897

ABSTRACT

OBJECTIVE@#To compare the clinical efficacy of acupoint catgut embedding and bupropion hydrochloride sustained-release tablets in the treatment of tobacco dependence.@*METHODS@#A total of 100 patients with tobacco dependence who met the inclusion criteria were randomly divided into an acupoint catgut embedding group and a drug group, 50 cases in each group. In the acupoint catgut embedding group, acupoint catgut embedding was applied at Xinshu (BL 15), Shenmen (HT 7), Tianmei (Extra), Taichong (LR 3), the treatment was given once every 2 weeks for 4 times; The bupropion hydrochloride sustained-release tablets was orally administered in the drug group for 7 weeks, 150 mg each time, once a day for the first 3 days, twice daily from day 4 to day 7, and once a day after day 8. The Fagerström test for nicotine dependence (FTND) score before and after treatment, the 4th and 8th week smoking cessation rate, the continuous smoking cessation rate and efficacy, compliance rate and adverse reaction rate were compared in the two groups.@*RESULTS@#A total of 100 patients were enrolled, and 97 patients completed the study (loss rate was 3%), including 49 cases in the acupoint catgut embedding group and 48 cases in the drug group. The FTND scores in the two groups were lower than those before treatment (both 0.05). At the 4th and the 8th week, the smoking cessation rate in the acupoint catgut embedding group was 40.8% (20/49) and 79.6% (39/49) respectively, the smoking cessation rate in the drug group was 41.7% (20/48) and 83.3% (40/48) respectively, the two groups were equally effective (both >0.05). The continuous smoking cessation rate in the acupoint embedding group was 40.8% (20/49), which was equivalent to 41.7% (20/48) in the drug group (>0.05). The rate of complete compliance in the acupoint embedding group was 61.2% (30/49), which was significantly better than 37.5% (18/48) in the drug group (<0.05). The adverse reaction rate in the acupoint catgut embedding group was 12.2% (6/49), which was significantly lower than 29.2% (16/48) in the drug group (<0.05).@*CONCLUSION@#Acupoint catgut embedding can effectively improve the symptoms of tobacco dependence after smoking cessation. Its curative effect is close to that of bupropion hydrochloride sustained-release tablets, and it has good clinical compliance and less adverse reactions.


Subject(s)
Acupuncture Points , Bupropion , Therapeutic Uses , Catgut , Delayed-Action Preparations , Humans , Tablets , Tobacco Use Disorder , Therapeutics
10.
Braz. oral res. (Online) ; 33: e086, 2019. tab, graf
Article in English | LILACS | ID: biblio-1019605

ABSTRACT

Abstract Treatment of patients with bisphosphonate usage is a significant concern for oral surgeons because it interferes with jaw bone turnover and regeneration. In case of adverse effects manifesting related to bisphosphonate use, oral surgeons are usually treating and keep the patient's symptoms under control. In this study, we aimed to investigate a new treatment protocol for medication-related osteonecrosis of the jaw (MRONJ). This treatment protocol consisted of administering human parathyroid hormone (hPTH) loaded chitosan microspheres which were prepared by ionotropic gelation method or/and the prepared microspheres were suspended in a poloxamer gel. After in-vitro optimization studies, the efficacy of the chosen formulations was evaluated in-vivo studies. Zoledronic acid was administered daily to forty-eight adult female Sprague-Dawley rats, divided into four experimental groups, at a daily concentration of 0.11 mg/kg over three weeks to induce the MRONJ model. At the end of this period, maxillary left molar teeth were extracted. In the first group, the subjects received no treatment. In the negative control group, poloxamer hydrogel containing empty microspheres were immediately applied to the soft tissues surrounding the extraction socket. The treatment group-1 was treated with local injections of poloxamer hydrogel containing hPTH. The treatment group-2 was treated with a single local injection of poloxamer hydrogel containing hPTH-loaded chitosan microspheres. Both treatment groups received a total of 7 µg of hPTH at the end of the treatment protocol. Our study demonstrates successful attenuation of MRONJ through a local drug delivery system combined with hPTH, as opposed to previously attempted treatment strategies.


Subject(s)
Humans , Animals , Female , Parathyroid Hormone/pharmacology , Chitosan/pharmacology , Bone Density Conservation Agents/pharmacology , Maxilla/drug effects , Parathyroid Hormone/therapeutic use , Rats, Sprague-Dawley , Poloxamer/administration & dosage , Poloxamer/chemistry , Models, Animal , Delayed-Action Preparations , Chitosan/therapeutic use , Bone Density Conservation Agents/adverse effects , Bone Density Conservation Agents/therapeutic use , Bisphosphonate-Associated Osteonecrosis of the Jaw , Bisphosphonate-Associated Osteonecrosis of the Jaw/drug therapy , Zoledronic Acid/adverse effects , Maxilla/pathology , Microspheres
11.
Article in English | WPRIM | ID: wpr-773613

ABSTRACT

In the present study, a gastric retention floating system for Brucea javanica oil, composed of alginate and carrageenan, was prepared using ionotropic gelation. Parameters for floatability, drug load, encapsulation efficiency, bead morphology, in vitro release, and in vivo gastric retention were evaluated. The optimized formulation via Box-Behnken design consisted of 1.7% alginate (W/V), 1.02% carrageenan (W/V), 1.4% CaCO (W/V), and a gelling bath of pH 0.8. The alginate-carrageenan-Brucea javanica oil beads had a porous structure and exhibited up to 24 h of in vitro floatability with a load capacity of 45%-55% and an encapsulation efficiency of 70%-80%. A 6-h sustained release was observed in vitro. The beads had a prolonged gastric retention (> 60% at 6 h) in fasted rats, compared to non-floating beads (15% at 6 h), as measured by gamma scintigraphy with single-photon emission tomography/computed tomography (SPET/CT). In conclusion, the alginate-carrageenan-Brucea javanica oil system showed enhanced oil encapsulation efficiency, excellent floating and gastric retention abilities, and a favorable release behavior.


Subject(s)
Alginates , Chemistry , Animals , Biological Availability , Brucea , Chemistry , Carrageenan , Chemistry , Delayed-Action Preparations , Chemistry , Pharmacokinetics , Drug Carriers , Chemistry , Drug Delivery Systems , Methods , Drug Evaluation, Preclinical , Gastric Mucosa , Metabolism , Glucuronic Acid , Chemistry , Hexuronic Acids , Chemistry , Microspheres , Plant Oils , Chemistry , Pharmacokinetics , Rats , Rats, Sprague-Dawley
12.
Article in English | WPRIM | ID: wpr-812402

ABSTRACT

In the present study, a gastric retention floating system for Brucea javanica oil, composed of alginate and carrageenan, was prepared using ionotropic gelation. Parameters for floatability, drug load, encapsulation efficiency, bead morphology, in vitro release, and in vivo gastric retention were evaluated. The optimized formulation via Box-Behnken design consisted of 1.7% alginate (W/V), 1.02% carrageenan (W/V), 1.4% CaCO (W/V), and a gelling bath of pH 0.8. The alginate-carrageenan-Brucea javanica oil beads had a porous structure and exhibited up to 24 h of in vitro floatability with a load capacity of 45%-55% and an encapsulation efficiency of 70%-80%. A 6-h sustained release was observed in vitro. The beads had a prolonged gastric retention (> 60% at 6 h) in fasted rats, compared to non-floating beads (15% at 6 h), as measured by gamma scintigraphy with single-photon emission tomography/computed tomography (SPET/CT). In conclusion, the alginate-carrageenan-Brucea javanica oil system showed enhanced oil encapsulation efficiency, excellent floating and gastric retention abilities, and a favorable release behavior.


Subject(s)
Alginates , Chemistry , Animals , Biological Availability , Brucea , Chemistry , Carrageenan , Chemistry , Delayed-Action Preparations , Chemistry , Pharmacokinetics , Drug Carriers , Chemistry , Drug Delivery Systems , Methods , Drug Evaluation, Preclinical , Gastric Mucosa , Metabolism , Glucuronic Acid , Chemistry , Hexuronic Acids , Chemistry , Microspheres , Plant Oils , Chemistry , Pharmacokinetics , Rats , Rats, Sprague-Dawley
13.
São Paulo; s.n; s.n; 2018. 116 p. tab, ilus, graf.
Thesis in Portuguese | LILACS | ID: biblio-997867

ABSTRACT

As Formas Farmacêuticas de Liberação Prolongada (FFLP) têm sido uma alternativa eficaz na terapia, pois proporcionam maior adesão do paciente ao tratamento em função da redução da frequência de dosagem ao longo do dia, sendo sua principal característica, a modulação da liberação/dissolução do fármaco. Entretanto, esta etapa pode ser influenciada por diferentes fatores, dentre eles: os físico-químicos relacionados ao fármaco; os farmacêuticos, principalmente relacionados aos excipientes empregados e às técnicas de obtenção da forma farmacêutica (FF) e os fisiológicos do trato gastrintestinal (TGI), como por exemplo, o pH dos líquidos do TGI, o tempo de esvaziamento gástrico, a motilidade intestinal, entre outros. Desse modo, a avaliação do trânsito da FF no TGI, após a sua administração, permite uma melhor compreensão dos fatores que podem afetar as etapas de liberação/dissolução do fármaco in vivo. Dentre as técnicas empregadas com esse objetivo, destacam-se: a cintilografia e os métodos biomagnéticos. A Biosusceptometria de Corrente Alternada (BAC) é um método biomagnético que tem se mostrado promissor para este tipo de estudo, por ser não invasivo, portátil, livre de radiação ionizante, e por apresentar acurácia e versatilidade. Diante do exposto, o presente trabalho teve como objetivos, desenvolver e caracterizar sob o aspecto biofarmacotécnico in vitro, um sistema de liberação prolongada contendo nimesulida (fármaco-modelo) e marcador magnético (ferrita), visando obtenção de ferramenta para avaliação do trânsito gastrintestinal por meio de técnica biomagnética. Para isto foram desenvolvidas quatro formulações de comprimidos de liberação prolongada contendo nimesulida, ferrita e diferentes concentrações de hidroxipropilmetilcelulose (HPMC): NF1 (30% HPMC); NF2 (23% HPMC); NF3 (17% HPMC) e NF4 (10% HPMC). Essas foram avaliadas quanto ao comportamento de dissolução por meio de ensaios com aparato 4 e avaliação da cinética e da eficiência de dissolução (ED%). Posteriormente, estudos biomagnéticos, in vitro e in vivo, foram conduzidos com emprego da técnica de BAC para a formulação selecionada. Os resultados obtidos mostraram que as 04 formulações desenvolvidas apresentaram porcentagens de dissolução distintas em função das diferentes concentrações de HPMC (NF1 = 13,2%; NF2 = 40,1%; NF3 = 72,5% e NF4 = 91,5%). A formulação NF4, com menor concentração de HPMC, foi escolhida para os estudos por meio de BAC em função dos resultados de ED% (54,3%) e por apresentar comportamento mais próximo de uma formulação de liberação prolongada. Em relação aos resultados de BAC in vitro, destaca-se que a formulação NF4 (10%HPMC) apresentou aumento de área magnética de forma independente do pH do meio, sugerindo que a hidratação/intumescimento da HPMC independe do pH. Em relação à avaliação do trânsito intestinal (estudo in vivo) foram obtidos os seguintes dados: Tempo médio de Residência Gástrica (TTR) - 89 minutos; Tempo médio do Trânsito Orocecal (TTO) - 313 minutos e Tempo médio do Trânsito Intestinal (TTI) - 224 minutos. Os dados de BAC in vivo permitiram observar que o aumento de área magnética atingiu um platô em cerca de 80 minutos após a administração da formulação NF4. A comparação dos dados de BAC in vitro e BAC in vivo, relacionados ao trânsito gastrintestinal, indica que a formulação NF4, após apresentar o ápice de intumescimento, foi capaz de manter sua estrutura permanente ao longo do TGI, favorecendo assim a liberação modulada do fármaco. Os resultados obtidos demonstraram que a formulação desenvolvida foi eficiente para avaliar e caracterizar o trânsito no TGI por meio da técnica de BAC e também permitiram uma estimativa do comportamento do fármaco em relação a solubilidade em cada porção do TGI, proporcionando assim uma ferramenta adequada para avaliação do trânsito do TGI e desenvolvimento de FFLP


Extended Release (ER) dosage forms have been an effective alternative in therapy, since they provide greater patient adherence to treatment as a function of the reduction of the frequency of dosing throughout the day, its main characteristic being the release / dissolution modulation of the drug. However, this stage can be influenced by different factors, among them: the physical and chemical related to the drug; the pharmacists, mainly related to the excipients employed and the techniques of obtaining the form dosage and the physiological ones of the gastrointestinal tract (GI tract), as for example, the pH of the liquid of the GI tract, gastric emptying time, intestinal motility, among others. Thus, assessment of dosage forms transit in GI tract after its administration allows a better understanding of the factors that may affect the drug release / dissolution steps in vivo. Among the techniques used for this purpose, the following stand out: scintigraphy and biomagnetic methods. Alternating Current Biosensiometry (ACB) is a biomagnetic method that has shown promise for this type of study, since it is non-invasive, portable, free of ionizing radiation, and because of its accuracy and versatility. In view of the above, the aim of this work was to develop and characterize a sustained release system containing nimesulide (study drug) and magnetic marker (ferrite) under the in vitro biopharmaceutical aspect, aiming to obtain a tool to evaluate the GI tract transit through means of biomagnetic technique. For this, four formulations of extended release tablets containing nimesulide, ferrite and different concentrations of hydroxypropylmethylcellulose (HPMC): NF1 (30% HPMC) were developed; NF2 (23% HPMC); NF3 (17% HPMC) and NF4 (10% HPMC). These were evaluated for dissolution behavior by apparatus 4, assays and kinetics and dissolution efficiency (ED%). Subsequently, biomagnetic studies, in vitro and in vivo, were conducted using the ACB technique for the selected formulation. The results showed that the formulations developed showed different percentages of dissolution as a function of the different concentrations of HPMC (NF1 = 13.2%, NF2 = 40.1%, NF3 = 72.5% and NF4 = 91.5%). The NF4 formulation, with a lower concentration of HPMC, was chosen for the ACB studies as a function of ED% results (54,3%) and because of the behavior of a sustained release formulation. In relation to the in vitro ACB results, the NF4 formulation (10% HPMC) showed an increase in magnetic area independently of the pH of the medium, suggesting that the HPMC hydration / swelling is independent of pH. In relation to intestinal transit evaluation (in vivo study) the following data were obtained: Mean Time of Gastric Residency (TTR) - 89 minutes; Mean Time of Orocecal Transit (OCTT) - 313 minutes and Mean Time of lntestinal Transit (TTI) - 224 minutes. ACB data in vivo showed that the increase in magnetic area reached a plateau in about 80 minutes after administration of the NF4 formulation. Comparison of in vitro ACB and ACB data in vivo, related to gastrointestinal transit, indicates that the NF4 formulation, after showing the swelling apex, was able to maintain its permanent structure throughout the GI tract, thus favoring the modulated release of the drug. The obtained results demonstrated that the developed formulation was efficient to evaluate and characterize the transit in the GI tract by means of the ACB technique and allowed a prediction of the behavior of the drug in relation to the solubility in each portion of the GI tract, thus providing a suitable tool for evaluation of the GI tract transit and the development of sustained release formulation


Subject(s)
Tablets/classification , Delayed-Action Preparations/analysis , In Vitro Techniques/instrumentation , Gastrointestinal Transit/physiology , Dissolution
14.
Braz. J. Pharm. Sci. (Online) ; 54(3): e17277, 2018. tab, graf
Article in English | LILACS | ID: biblio-974420

ABSTRACT

The purpose of the study is to develop cephalexin controlled-release matrix tablets by using lower proportions of release retardant polymer and to establish their in vitro & in vivo correlation. Tablets were compressed by incorporating polymers in a matrix form along with drug which prolong the drug release. Twelve formulations were prepared by mixing ethyl cellulose (EC) and hydroxypropyl methylcellulose (HPMC) (three different viscosity grades) in various proportions. F-1 to F-4 formulations were prepared by incorporating drug, HPMC K4M and ethyl cellulose in 100 : 5 : 5, 100 : 10 : 5, 100 : 15 : 5 and 100 : 20 : 5; similarly, F-5 to F-8 were prepared with HPMC K15M; and F-9 to F-12 were prepared with HPMC K100M using a wet granulation process maintained same proportions, along with drug and EC. Tablets were evaluated for their pre-compression and post-compression characteristics and they were found to be in limits. From the dissolution testing, F-4 showed 100.34% medicament release in 12 h. In vivo studies were conducted on rabbit and pharmacokinetic parameters of the optimized formulation were evaluated using HPLC method. It was found that matrix tablets showed increased t1/2 and decreased Kel. The design signified that the drug release rate from tablets was influenced by the small proportion (around 7% of a tablet weight) of polymer mixture and it controlled 100% medicament release upto 12 h effectively with the low grade viscosity of HPMC combination, with good in vitro & in vivo correlation.


Subject(s)
Tablets/analysis , In Vitro Techniques/instrumentation , Cephalexin/analysis , Polymers , Chromatography, High Pressure Liquid/methods , Delayed-Action Preparations , Drug Compounding
15.
Rev. argent. salud publica ; 8(33): 35-40, Dic. 2017. tab
Article in Spanish | LILACS | ID: biblio-883187

ABSTRACT

El tratamiento inmunosupresor es uno de los pilares del éxito luego de un trasplante de órganos. El tacrolimus (fármaco de la familia de los inhibidores de la calcineurina) es una de las drogas más utilizadas luego de un trasplante. La hipótesis de que la forma farmacéutica de liberación prolongada es superior a la de liberación inmediata, de uso habitual, es analizada en el presente trabajo.


Subject(s)
Delayed-Action Preparations , Graft Rejection , Immunosuppression , Tacrolimus
16.
Int. braz. j. urol ; 43(4): 713-720, July-Aug. 2017. tab
Article in English | LILACS | ID: biblio-892881

ABSTRACT

ABSTRACT Introduction Overactive bladder (OAB) is a common condition, especially in middle aged women, requiring long term therapy with anticholinergics to maintain symptoms relief. The aim of the study was to determine the effect of tolterodine extended release (ER) used for OAB treatment on the sexual function of women. Materials and Methods Between August 2010 and August 2014, 220 women with confirmed OAB, attended Urogynecology Outpatient Clinic and were prospectively enrolled in this study. 158 women were evaluated, with a comprehensive history, physical examination, urodynamic studies and Female Sexual Function Index (FSFI) questionnaire. 73 patients of group A (control group) received no treatment and 85 patients of group B received an anticholinergic regimen - tolterodine ER 4mg once daily. Data were evaluated again in accordance with FSFI after three months, using SPSS software. Results A statistically significant increase was noted in group B in domains of desire (pre-treatment 2.5±0.2 to 4.5±0.2 post-treatment), arousal (3.1±0.2 to 3.1±0.2 respectively), lubrication (3.4±0.3 to 4.3±0.3 respectively), orgasm (3.5±0.3 to 4.5±0.3 respectively), satisfaction (2.6±0.2 to 4.2±0.3 respectively) and pain (2.4±0.2 to 4.6±0.4 respectively) after three months treatment with tolterodine ER. In group A there were no statistically significant changes in pre and post treatment values (p>0.05). Total FSFI score for group B was significantly higher after tolterodine treatment (26.5±1.5) compared to pre-treatment values (17.4±1.4, p<0.01) and to control group A (17.7±1.2 and 17.9±1.5, p>0,05) respectively. Conclusions This preliminary study demonstrates that treatment of OAB with tolterodine ER was found to have positive effect on sexual function of patients with OAB.


Subject(s)
Humans , Female , Adult , Young Adult , Sexual Behavior/drug effects , Sexual Dysfunction, Physiological/drug therapy , Urinary Bladder, Overactive/drug therapy , Urological Agents/therapeutic use , Tolterodine Tartrate/therapeutic use , Prospective Studies , Surveys and Questionnaires , Delayed-Action Preparations , Urological Agents/adverse effects , Tolterodine Tartrate/adverse effects , Middle Aged
18.
Article in English | WPRIM | ID: wpr-812041

ABSTRACT

As the carrier of water-insoluble drugs, microspheres can play a role in increasing solubility and delaying releasing essence. The objective of this study was to improve the solubility and to delay the release of a newly discovered antitumor compound 3β-hydroxyolea-12-en-28-oic acid-3, 5, 6-trimethylpyrazin-2-methyl ester (T-OA). Early-stage preparation discovery concept (EPDC) was employed in the present study. The preparation, physicochemical characterization, and drug release properties of PLGA microspheres were evaluated. T-OA-loaded PLGA microspheres were prepared by an oil-in-water (O/W) emulsification solvent evaporation method. Characterization and release behaviors of the T-OA PLGA microspheres were evaluated by X-ray diffract (XRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and high performance liquid chromatography (HPLC). The results demonstrated that T-OA-loaded PLGA microspheres could be successfully obtained through solvent evaporation method with appropriate morphologic characteristics and high encapsulation efficiency. The XRD analysis showed that T-OA would be either molecularly dispersed in the polymer or distributed in an amorphous form. The DSC and FTIR analysis proved that there were interactions between T-OA and PLGA polymer. SEM observations displayed the morphology of the microspheres was homogeneous and the majority of the spheres ranged between 50 and 150 μm. The drug release behavior of the microspheres in the phosphate buffered saline medium exhibited a sustained release and the duration of the release lasted for more than 23 days, which was fit with zero-order release pattern with r = 0.9947. In conclusion, TOA-loaded PLGA microspheres might hold great promise for using as a drug-delivery system in biomedical applications.


Subject(s)
Antineoplastic Agents , Chemistry , Calorimetry, Differential Scanning , Chemistry, Pharmaceutical , Delayed-Action Preparations , Chemistry , Drug Carriers , Chemistry , Lactic Acid , Chemistry , Microscopy, Electron, Scanning , Microspheres , Oleanolic Acid , Chemistry , Polyglycolic Acid , Chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Pyrazines , Chemistry , Solubility , Spectroscopy, Fourier Transform Infrared , X-Ray Diffraction
19.
National Journal of Andrology ; (12): 1107-1110, 2017.
Article in Chinese | WPRIM | ID: wpr-812825

ABSTRACT

Objective@#To study the therapeutic effect of Lamiophlomis Rotata Capsule (LRC) in the treatment of type ⅢB prostatitis.@*METHODS@#We randomly divided 225 patients with type ⅢB prostatitis into an experimental group (n =125) and a control group (n =120), the former treated orally with LRC at 3 capsules tid while the latter with tamsulosin hydrochloride sustained-release capsules at 0.2 mg qd, both for 4 weeks. We compared the therapeutic effects between the two groups of patients based on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) obtained before, immediately after and at 4 weeks after medication.@*RESULTS@#A total of 120 patients completed the treatment in the experimental group, which showed remarkable decreases as compared with the baseline in the pain score (5.30 ± 1.23 vs 14.68 ± 1.51, P0.05). The experimental group achieved even markedly lower scores than the controls in the pain symptom (5.30 ± 1.23 vs 13.67 ± 1.49, P<0.05), QoL (6.46 ± 0.93 vs 7.47 ± 0.88, P<0.05) and total NIH-CPSI (17.50 ± 2.77 vs 25.77 ± 2.01, P<0.05) but a higher urination symptoms score than the latter after medication (7.16 ± 1.04 vs 5.68 ± 1.34, P<0.05). At 4 weeks after drug withdrawal, the experimental group also showed significantly lower scores of the pain symptom (7.23 ± 1.03), QoL (6.58 ± 0.87) and total NIH-CPSI (22.18 ± 2.03) than the baseline (all P<0.05) and those in the control group (14.14 ± 0.98, 8.12 ± 0.72 and 26.89 ± 1.67) (all P<0.05). Apart from dizziness in 2 of the patients, who gave up medication halfway, no other obvious adverse reactions were observed during the experiment.@*CONCLUSIONS@#Lamiophlomis Rotata Capsule deserves to be recommended for the treatment of type ⅢB prostatitis for its safety and effectiveness in reducing the pain and improving the life quality of the patients.


Subject(s)
Capsules , Chronic Disease , Delayed-Action Preparations , Drugs, Chinese Herbal , Therapeutic Uses , Humans , Male , Pain Management , Prostatitis , Drug Therapy , Pathology , Quality of Life , Tamsulosin , Therapeutic Uses , Urination , Urological Agents , Therapeutic Uses
20.
National Journal of Andrology ; (12): 164-168, 2017.
Article in Chinese | WPRIM | ID: wpr-812792

ABSTRACT

Objective@#To study the safety and efficacy of Bushen Daozhuo Granules (BDG) in the treatment of type Ⅲ prostatitis.@*METHODS@#This multicenter randomized controlled clinical trial included 478 patients with type Ⅲ prostatitis, 290 in the trial group and 188 as controls, the former treated with BDG at 200 ml bid and the latter with tamsulosin hydrochloride sustainedrelease capsules at 0.2 mg qd, both for 4 weeks. Before treatment, after 4 weeks of medication, and at 4 weeks after drug withdrawal, we obtained the NIH Chronic Prostatitis Symptom Index (NIHCPSI) scores and compared the safety and effectiveness rate between the two groups of patients.@*RESULTS@#Compared with the baseline, the NIHCPSI score was markedly decreased in the control group after 4 weeks of medication (21.42 ± 4.02 vs 15.67 ± 3.65, P 0.05), while the NIHCPSI score in the trial group was remarkably lower than the baseline both after 4 weeks of medication and at 4 weeks after drug withdrawal (10.92 ± 2.06 and 12.91 ± 2.64 vs 21.58 ± 3.67, P < 0.05). The trial group exhibited both a higher rate of total effectiveness and safety than the control (P < 0.05).@*CONCLUSIONS@#BDG is safe and effective for the treatment of type Ⅲ prostatitis.


Subject(s)
Capsules , Chronic Disease , Delayed-Action Preparations , Drugs, Chinese Herbal , Therapeutic Uses , Humans , Male , Prostatitis , Drug Therapy , Pathology , Sulfonamides , Therapeutic Uses , Tamsulosin , Treatment Outcome , Urological Agents , Therapeutic Uses
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