Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 38
Filtrar
1.
Food Chem X ; 13: 100220, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35498959

RESUMO

Agroscope Culture Collection was screened to identify bacterial strains effective in production of dairy flavor inducing lactones using grapeseed oil as a substrate. Lentilactobacillus parafarraginis FAM-1079, Lactococcus lactis subsp. lactis FAM-17918, and L. lactis subsp. lactis biovar diacetylactis FAM-22003 showed the most efficient formation of targeted δ-lactones. The application of sublethal heat stress significantly increased target lactone production. The most profound improvement was for L. lactis subsp. lactis biovar diacetylactis where δ-octadecalactone generation was improved by factor of 9. The pre-fermentation step as well as growth phase in which bacteria are harvested did not have a significant impact on lactones yield. The lactone production process from vegetable oil developed in this study offers a new way of developing a natural flavor ingredient for incorporation into plant-based products.

2.
Acta Gastroenterol Belg ; 80(2): 257-261, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29560691

RESUMO

BACKGROUND: Anecdotally, we observed that patients who had previous colonoscopies were less likely to follow newly implemented split-dose bowel preparation (SDBP) instructions. We investigated whether the indication for colonoscopy is an independent factor for achieving high quality bowel preparation among patients asked to follow SDBP. METHODS: We performed a retrospective study of data from 1478 patients who received outpatient colonoscopies in 2014 (the year of SDBP implementation) at our Veterans Affairs Medical Center. We collected information related to demographics and factors known to affect bowel preparations. Reasons for colonoscopy were dichotomized into surveillance (previous colonoscopy) vs. non-surveillance (positive occult blood test or screening). Bowel preparation quality was scored using the Boston Bowel Preparation Scale (BBPS), and was categorized as either excellent vs. not excellent (BBPS≥7 vs. BBPS<7), or adequate vs. inadequate (BBPS≥6 vs. BBPS<6). RESULTS: Bowel preparation quality was excellent in 60% of colonoscopies and adequate in 84% of colonoscopies. Thirty-six percent (535) were surveillance colonoscopies. In multivariate logistic regression analysis, more patients in the non-surveillance group achieved excellent (OR 0.8 ; 95% CI [0.7-0.8], P <0.0001) and adequate (OR 0.8 ; 95% CI [0.7-0.9], P <0.006) bowel preparation than did patients in the surveillance group. CONCLUSION: Patients with a prior colonoscopy might not follow the split-dose bowel preparation instructions. Educational interventions emphasizing the benefits of SDBP in this group of patients may help ensure compliance and prevent the habitual use of day-before preparations.


Assuntos
Catárticos/administração & dosagem , Colonoscopia , Cooperação do Paciente , Educação de Pacientes como Assunto , Idoso , Colonoscopia/métodos , Colonoscopia/psicologia , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Cooperação do Paciente/psicologia , Cooperação do Paciente/estatística & dados numéricos , Melhoria de Qualidade , Estudos Retrospectivos , Estados Unidos
3.
Transplant Proc ; 43(2): 598-600, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21440773

RESUMO

PURPOSE: Recurrence of hepatitis B virus after a liver transplantation (OLT) is a risk factor affecting graft and patient survivals. Short-term hepatitis B virus reactivation rates after OLT range between 3% and 15%. Using combination prophylaxis, the outcomes of OLT among patients with liver disease related to hepatitis B virus have improved to levels comparable to those whose disease is not related to hepatitis B virus. MATERIALS AND METHODS: Since September 2001, we performed 288 OLT in 282 patients including 74 who had liver failure related to hepatitis B virus among whom 58 were followed for >12 months and analyzed retrospectively. Our protocol included lamivudine (100 mg orally per day beginning the day after surgery) and hepatitis B immunoglobulin (10,000 IU IV during the anhepatic phase, 2000 IU/d IV during the first week after surgery, 2000 IU IV/month from postoperative months 1 to 12). Using our protocol, the anti-hepatitis B surface antibodies (HBsAb) serum titer was maintained up to 100 IU/mL. The female:male ratio was 11:47. The mean age of patients was 43±12.8 years. RESULTS: Five patients died of causes unrelated to hepatitis B virus. At the time of death, their hepatitis B surface antigens were negative, and serum titers of anti-HBsAb were 45, 35.3, 56.4, 79.6, and 123 IU/mL. Mean follow-up was 46.5±18.9 months (range, 12-79). The hepatitis B surface antigen became positive in 4 patients; the remaining 49 had no evidence of hepatitis B surface antigen. In 18 patients, serum titer of anti-hepatitis B surface antigen was 0; in the remaining 31 patients, it was 69.2±133 IU/mL. CONCLUSION: Our combination protocol with hepatitis B immunoglobulin and lamivudine is a safe, cost-saving, and effective treatment for hepatitis B virus prophylaxis after liver transplantation.


Assuntos
Hepatite B/sangue , Hepatite B/prevenção & controle , Imunoglobulinas/imunologia , Lamivudina/farmacologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Antígenos de Superfície da Hepatite B/química , Humanos , Falência Hepática/complicações , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Inibidores da Transcriptase Reversa/farmacologia , Fatores de Risco
4.
Int J Androl ; 33(6): 861-4, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20050938

RESUMO

To evaluate the efficacy of sildenafil in the treatment of neurogenic erectile dysfunction (ED) secondary to upper motor neuron (UMN) and lower motor neuron (LMN) spinal cord injury (SCI). After taking consents 105 patients suffering from ED were enrolled in this prospective study. Seventy-two patients had signs and symptoms of UMN and 33 patients had signs and symptoms of LMN or mixed (UMN and LMN) spinal cord injuries. The patients took 50-100 mg sildenafil or placebo tablet at least 45 min before sexual intercourse. Based on a IIEF questionnaire, success in achieving erection adequate for sexual intercourse was compared between sildenafil and placebo groups in UMN and non-UMN spinal cord injuries. In patients with UMN disease, sildenafil was effective in 82% of patients and its efficacy was statistically higher than placebo (82 vs. 25%, p < 0.05). Twenty-eight per cent of patients with non-UMN disease had a favourable response to sildenafil that was not statistically different from placebo. Sildenafil seems more effective in the treatment of neurogenic ED secondary to UMN spinal cord injury compared with that secondary to LMN injury. Actually, its efficacy on LMN injuries does not seem different from placebo and administration of this treatment may not be effective in spinal cord injury which has caused LMN symptoms.


Assuntos
Disfunção Erétil/tratamento farmacológico , Paraplegia/complicações , Inibidores de Fosfodiesterase/uso terapêutico , Piperazinas/uso terapêutico , Traumatismos da Medula Espinal/complicações , Sulfonas/uso terapêutico , Adulto , Disfunção Erétil/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Purinas/uso terapêutico , Citrato de Sildenafila
5.
Drug Deliv ; 14(7): 413-26, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17994358

RESUMO

The primary objective of this study was to compare the lubrication properties of micronized poloxamer 188 (Lmicrotrol micro 68) and micronized poloxamer 407 (Lmicrotrol micro 127) with certain conventional lubricants such as magnesium stearate and stearic acid. The secondary objective was to use these micronized poloxamers as water-soluble tablet lubricants in preparation of effervecsent tablets. The results showed that these micronized poloxamers have superior lubrication properties compared with stearic acid, with no negative effect on tablet hardness, friability, disintegration, or dissolution. Moreover, lubricant mixing time had no significant effect on tablet properties when poloxamers were used as lubricants. Effervescent tablets also were produced successfully using micronized poloxamers as lubricants. The micronized poloxamers had a better lubrication effect in comparison with that of water-soluble lubricant l-leucine.


Assuntos
Excipientes/química , Lubrificantes/química , Poloxâmero/química , Acetaminofen/química , Aspirina/química , Cafeína/química , Química Farmacêutica , Dureza , Interações Hidrofóbicas e Hidrofílicas , Leucina/química , Solubilidade , Ácidos Esteáricos/química , Propriedades de Superfície , Comprimidos
6.
Drug Deliv ; 13(2): 121-31, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16423800

RESUMO

Kollicoat SR 30D is a unique 30% aqueous dispersion of polyvinvyl acetate stabilized by polyvinyl-pyrrolidone intended for preparation of sustained release products. Detailed evaluation of this polymer dispersion as a sustained release coating for active pharmaceutical ingredients of two diverse classes of drugs was studied. A water insoluble drug (ibuprofen) and a water soluble drug (ascorbic acid) were selected as model active drugs. Ibuprofen was granulated using a GPCG-1 fluid bed processor prior to tableting, to improve the particle size and particle flow properties. In this process a 2(3) factorial design was implemented to evaluate the optimum process parameters such as spray rate, inlet air temperature and the inlet air velocity. The statistical model selected was Y(ijkl) = mu + tau(i) + beta(j) + theta(k) + (taubeta)ij + (betatheta)jk + (tautheta)ik + (taubetatheta)ijk + epsilon(ijkl). The factorial design showed that the spray rate, inlet air temperature, and inlet air velocity had a significant effect (p value <0.05) on the particle size. Significant improvement was observed in the flow properties of the granules. The granules were coated with Kollicoat SR30D dispersion using top spray method in the fluid bed processor. The dissolution studies showed that the release of ibuprofen decreased with an increase in the coating levels of Kollicoat SR 30 D. In the case of ascorbic acid, preparation of sustained release coated commercial granules was not possible due to the difficulty in coating a highly soluble drug particle. However, the coated granules when compressed into tablets showed some sustainability. Ibuprofen tablets manufactured with coated granules with a 15 g polymer for 300 g batch showed dissolution parameters of t50 and t90 at 4.2 hr and 7.5 hr, respectively. An approximate zero-type of release was observed when the polymer content was increased to 45 g for 300 g batch. Ascorbic acid tablets made with coated commercial granules having a total polymer content of 45 g per a 500 g batch showed an average dissolution t50 and t90 at 1.0 hr and 4.55 hr, respectively. When the total polymer content was increased to 60 g, per 500 g, the average dissolution t50 and t90 delayed to 1.40 hr and 7.20 hr, respectively.


Assuntos
Preparações de Ação Retardada/farmacocinética , Polivinil/química , Análise de Variância , Ácido Ascórbico/química , Ácido Ascórbico/farmacocinética , Preparações de Ação Retardada/química , Ibuprofeno/química , Ibuprofeno/farmacocinética , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Polivinil/farmacocinética , Reprodutibilidade dos Testes , Comprimidos , Tecnologia Farmacêutica/métodos
7.
Indian J Clin Biochem ; 21(1): 177-80, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23105594

RESUMO

Urinary abnormalities were evaluated in 100 renal stone patients with first episode of renal stone having age 22 to 45 years from both sex and compared to 100 normal healthy control group having same age group from both sex. Twenty-four hours urinary oxalate, calcium, uric acid, sodium, magnesium, phosphorus and citrate were estimated. The urinary pH was also determined. In stone formers urinary oxalate, calcium, sodium and uric acid excretions were significantly higher when compared with control group. Whereas citrate, phosphate and magnesium excretion were significantly lower in stone formers when compared with control.The pH of urine in stone formers was lower than the controls. High dietary intake of purine rich diet causes elevated excretion of uric acid, which leads to calcium oxalate crystal formation and precipitation. Other risk factors such as urinary oxalate, calcium also related to formation of renal calculi.Hypocitraturia is the main cause of renal calculi along with hypomagnesiuria and hypophosphaturia in the patient of Marathwada region. On the basis of urinary abnormalities further stone formation in the patient can be prevented by dietary modifications.

9.
Anticancer Res ; 21(3B): 1749-55, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11497255

RESUMO

The effects of indomethacin on A/J mice were investigated. The non-steroidal antiinflammatory drug (NSAID) indomethacin reduced significantly the number of lung adenomas 3, 4 or 8 months after urethane injection by 28, 30 and 29% respectively. The density of apoptotic cell bodies increased 2.9-fold in the lung adenomas of A/J mice treated with indomethacin. By immunocytochemistry, COX-2 immunoreactivity was present in the cytosol of lung adenomas, and in epithelial cells lining the bronchioli and bronchus as well as type 2 alveolar cells. COX-1 immunostaining was similar to that of COX-2 in the lungs of urethane-injected mice treated with or without indomethacin. By RT-PCR, COX-1 and COX-2 PCR products were present in mouse lung adenomas, alveoli and bronchioli. These results suggest that indomethacin may inhibit COX-1 and COX-2 in the A/J mouse lung resulting in reduced adenoma formation.


Assuntos
Adenoma/tratamento farmacológico , Anti-Inflamatórios não Esteroides/farmacologia , Indometacina/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Adenoma/induzido quimicamente , Animais , Apoptose , Brônquios/metabolismo , Carcinógenos , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Citosol/metabolismo , Células Epiteliais/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Isoenzimas/biossíntese , Neoplasias Pulmonares/induzido quimicamente , Proteínas de Membrana , Camundongos , Prostaglandina-Endoperóxido Sintases/biossíntese , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Células Tumorais Cultivadas , Uretana
10.
Life Sci ; 66(5): 379-87, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10670826

RESUMO

The effects vasoactive intestinal peptide (VIP) antagonists were investigated on pancreatic cancer cell lines. (N-Stearyl, Norleucine17) VIP hybrid ((SN)VIPhyb) inhibited 125I-VIP binding to human Capan-2 cells with an IC50 value of 0.01 microM whereas VIP hybrid had an IC50 value of 0.2 microM. By RT-PCR and Northern blot, VPAC1 receptor mRNA was detected in CAPAN-2 cells. One microM (SN)VIPhyb and 10 microM VIPhyb inhibited the ability of 30 nM VIP to elevate cyclic AMP and increase c-fos mRNA. (SN)VIPhyb, 1 microM inhibited the clonal growth of CAPAN-2 cells in vitro. In vivo, (SN)VIPhyb (10 microg/day s.c.) inhibited CAPAN-2 xenograft growth in nude mice. These results indicate that (SN)VIPhyb is a pancreatic cancer VPAC receptor antagonist.


Assuntos
Neoplasias Pancreáticas/patologia , Receptores de Peptídeo Intestinal Vasoativo/antagonistas & inibidores , Peptídeo Intestinal Vasoativo/farmacologia , Sequência de Aminoácidos , Animais , Ligação Competitiva , Divisão Celular/efeitos dos fármacos , AMP Cíclico/metabolismo , Genes fos/genética , Humanos , Concentração Inibidora 50 , Camundongos , Camundongos Nus , Dados de Sequência Molecular , Transplante de Neoplasias , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Peptídeo Intestinal Vasoativo/genética , Receptores de Peptídeo Intestinal Vasoativo/metabolismo , Receptores Tipo I de Polipeptídeo Intestinal Vasoativo , Transplante Heterólogo , Células Tumorais Cultivadas , Peptídeo Intestinal Vasoativo/antagonistas & inibidores , Peptídeo Intestinal Vasoativo/metabolismo , Peptídeo Intestinal Vasoativo/uso terapêutico
11.
Drug Deliv ; 7(4): 223-9, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11195429

RESUMO

Ketorolac tromethamine is a potent non-narcotic analgesic with moderate anti-inflammatory activity. Clinical studies indicate that ketorolac has a single dose efficacy greater than morphine for postoperative pain and has excellent applicability in the emergency treatment of pain. Due to incomplete oral absorption of ketorolac, several approaches have been tried to develop a nonoral formulation in addition to injections, especially for the treatment of migraine headache. The aim of our study was to develop a nasal formulation of ketorolac with a dose equivalent to the oral formulation. A series of spray and lyophilized powder formulations of ketorolac were administered into the nasal cavity of rabbits, and their pharmacokinetics profiles were assessed. The spray and powder formulations were compared through their pharmacokinetics parameters and absolute bioavailability. Drug plasma concentration was determined using solid phase extraction, followed by an HPLC analysis. Nasal spray formulations were significantly better absorbed than powder formulations. A nasal spray formulation of ketorolac tromethamine showed the highest absorption with an absolute bioavailability of 91%. Within 30 min of administration, the plasma concentration was comparable to that resulting from an intravenous injection. The absolute bioavailability of a solution of ketorolac acid was 70%. Apparently, the dissolution of ketorolac acid into the mucous layer limits its absorption. There were no significant differences in absorption between different powder formulations. Even the reduction of particle size from 123 microm to 63 microm did not indicate better absorption of ketorolac tromethamine from powder formulations. Interestingly, the absolute bioavailability of ketorolac tromethamine from a powder formulation is only 38%, indicating that the drug may not be totally released from the polymer matrix before it is removed from nasal epithelium by mucociliary clearance.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Cetorolaco de Trometamina/administração & dosagem , Administração Intranasal , Análise de Variância , Animais , Anti-Inflamatórios não Esteroides/sangue , Anti-Inflamatórios não Esteroides/farmacocinética , Área Sob a Curva , Disponibilidade Biológica , Celulose , Excipientes , Injeções Intravenosas , Cetorolaco de Trometamina/sangue , Cetorolaco de Trometamina/farmacocinética , Masculino , Microesferas , Tamanho da Partícula , Coelhos
12.
Prog Retin Eye Res ; 17(1): 33-58, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9537794

RESUMO

Eye-drops are the conventional dosage forms that account for 90% of currently accessible ophthalmic formulations. Despite the excellent acceptance by patients, one of the major problems encountered is rapid precorneal drug loss. To improve ocular drug bioavailability, there is a significant effort directed towards new drug delivery systems for ophthalmic administration. This chapter will focus on three representative areas of ophthalmic drug delivery systems: polymeric gels, colloidal systems, cyclodextrins and collagen shields. Hydrogels generally offer a moderate improvement of ocular drug bioavailability with the disadvantage of blurring of vision. In situ activated gel-forming systems are preferred as they can be delivered in drop form with sustained release properties. Colloidal systems including liposomes and nanoparticles have the convenience of a drop, which is able to maintain drug activity at its site of action and is suitable for poorly water-soluble drugs. Among the new therapeutic approaches in ophthalmology, cyclodextrins represent an alternative approach to increase the solubility of the drug in solution and to increase corneal permeability. Finally, collagen shields have been developed as a new continuous-delivery system for drugs that provide high and sustained levels of drugs to the cornea, despite a problem of tolerance. It seems that new tendency of research in ophthalmic drug delivery systems is directed towards a combination of several drug delivery technologies. There is a tendency to develop systems which not only prolong the contact time of the vehicle at the ocular surface, but which at the same time slow down the elimination of the drug. Combination of drug delivery systems could open a new directive for improving results and the therapeutic response of non-efficacious systems.


Assuntos
Sistemas de Liberação de Medicamentos/tendências , Soluções Oftálmicas/administração & dosagem , Animais , Disponibilidade Biológica , Curativos Biológicos , Colágeno , Coloides , Ciclodextrinas , Portadores de Fármacos , Olho/efeitos dos fármacos , Olho/metabolismo , Géis , Humanos , Soluções Oftálmicas/farmacocinética
13.
J Microencapsul ; 15(2): 197-205, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9532525

RESUMO

The nasal route has received a great deal of attention due to the many advantages of nasal delivery over parenteral administration. The male sex hormone testosterone is ineffective when administered orally due to its gut wall and first-pass metabolism. Therefore, an alternative method for delivery would be the intranasal route, if the lack of aqueous solubility can be overcome. In this study a new approach to emulsion formulations of the drug has been proposed based on the hypothesis that increased absorption is possible upon solubilization of the drug and/or prolongation of the formulation residence time in the nose. Three differently charged testosterone submicron size emulsion formulations with various zeta potentials (+24.8, -23.0 and 0.06 mV) were prepared as nasal spray formulations. A dose of approximately 3.8 mg testosterone per rabbit was administered to four rabbits and the bioavailability of the emulsion formulations was assessed and compared with an i.v. formulation via solid-phase extraction, followed by an HPLC analysis method. Statistical analysis of the normalized data indicated a bioavailability of 55, 51 and 37% for positively, negatively and neutrally charged emulsions respectively. The results of this study strongly suggest that emulsion formulations have some potential to be considered for nasal delivery. Further, both the positively and negatively charged emulsion formulations provided a better bioavailability than the neutral charged emulsion, probably indicating that the charged particle interactions between emulsion globules and the mucus layer prolong the contact of drug with nasal membrane thus enhancing drug absorption.


Assuntos
Administração Intranasal , Composição de Medicamentos/métodos , Emulsões/química , Testosterona/química , Absorção/fisiologia , Animais , Disponibilidade Biológica , Química Farmacêutica , Sistemas de Liberação de Medicamentos/métodos , Injeções Intravenosas , Tamanho da Partícula , Coelhos , Solubilidade , Eletricidade Estática , Testosterona/farmacocinética
14.
Drug Deliv ; 5(2): 127-34, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-19570004

RESUMO

The objective of this investigation was to study the effect of the phospholipid dimyristoylphosphatidylglycerol (DMPG) on the intranasal absorption of the polypeptide salmon calcitonin (sCT). DMPG was included as an absorption enhancer for salmon calcitonin in a 0.03 M acetate buffer at pH 4 in a nasal spray formulation. The absorption of sCT was studied as a function of NaCl concentration from 0.045 to 0.3 M. Serum calcitonin was determined using a double-antibody radioimmunoassay (RIA). The presence of the phospholipid demonstrated a significant difference in the intranasal bioavailability of salmon calcitonin. The results showed that DMPG enhanced the nasal absorption of sCT by approximately twofold at a salt concentration of 0.045 M. However, higher salt concentrations in the formulation demonstrated a decrease in the absorption-enhancing effect of DMPG. The effect of DMPG on the calcium-lowering effect of sCT was also studied. There was no significant difference in the hypocalcemic activity of sCT in the presence of DMPG. In addition, it was found that increasing the viscosity of those formulations containing DMPG did not further increase the nasal bioavailability of sCT.

15.
Int J Pharm Compd ; 2(5): 390-3, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-23989705

RESUMO

Ketorolac tromethamine suppositories (30 mg) and ketoprofen suppositories (50 mg) were made by the fusion method with various bases such as cocoa butter, Witepsol H15, Witepsol W25, Witepsol W35, Witepsol E75, Suppocire AML and Hydrokote AP5-1. Also, ketorolac tromethamine and ketoprofen suppositories were prepared using Eudragit L100 and propylene glycol. The release rates for both ketorolac tromethamine and ketoprofen suppositories in Sorensen's phosphate buffer pH 7.4 were determined and found to be: cocoa butter greater than Witepsol H15 greater than Witepsol W25 greater than Suppocire AML greater than witepsol W35 greater than Hydrokote AP5-1> Witepsol E75. Drug-release studies showed that ketorolac tromethamine demonstrates faster release profiles from these selected bases in comparison to those seen for ketoprofen. Analysis of the relaease kinetics for ketorolac tromethamine and ketoprofen from the various bases suggests that a combination of release mechanisms such as melting of the base followed by partititoning of the drug, along with some diffusion of the drug from the base to the dissolution media, seems to be operative in these systems. The absolute bioavailabilty of the suppository formulaion made with ketorolac tromethamine in cocoa butter base was found to be 61% in rabbits.

16.
Eur J Pharm Biopharm ; 46(3): 265-71, 1998 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-9885297

RESUMO

The in vitro percutaneous fluxes of propylene glycol (PG), cis-oleic acid (OA) and dimethyl isosorbide (DI) were determined and their effect on nifedipine (N) flux and lag time evaluated. PG, OA and DI flux through hairless mouse (HM) skin was measured in vitro by beta-scintigraphy and N permeation was measured by HPLC under finite and infinite dose conditions. Evaluation of each of the solvents separately showed that pure DI possessed the inherent ability to traverse the skin (12% in 24 h). For the tested formulation after 24 h, 57% of the PG and 40% of the DI had permeated across the skin with nearly linear permeation between 4 and 18 h and the relative order of permeation was PG > DI > N. DI permeation was further aided in the presence of PG and OA. N flux was dependent on concomitant solvent permeation. Over a 24-h test period a dose dependent response was observed for N, with 4.9-15.6 mg of N delivered from the lowest and highest doses, respectively, and the highest dose yielding zero-order flux of 146 (g/h per cm2).


Assuntos
Isossorbida/análogos & derivados , Veículos Farmacêuticos/farmacocinética , Propilenoglicol/farmacocinética , Absorção Cutânea/efeitos dos fármacos , Animais , Bloqueadores dos Canais de Cálcio/farmacocinética , Radioisótopos de Carbono , Química Farmacêutica , Difusão , Sinergismo Farmacológico , Feminino , Técnicas In Vitro , Isossorbida/farmacocinética , Isossorbida/farmacologia , Camundongos , Camundongos Pelados , Nifedipino/farmacocinética , Ácido Oleico/farmacocinética , Ácido Oleico/farmacologia , Excipientes Farmacêuticos/farmacocinética , Excipientes Farmacêuticos/farmacologia , Veículos Farmacêuticos/farmacologia , Propilenoglicol/farmacologia , Reprodutibilidade dos Testes , Solubilidade
17.
J Microencapsul ; 14(4): 457-67, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9229345

RESUMO

The purpose of this study was to evaluate, in an ex-vivo study, the absorption of cyclosporine A on bovine cornea after 24 h contact with various drug delivery systems containing 1% cyclosporine A and in comparison with an olive oil formulation as the reference vehicle for cyclosporine A. The different formulations studied were poly(acrylic acid) polymeric gels in aqueous/non-aqueous solvents, polyisobutylcyanoacrylate nanocapsules, and a combination of both formulations. The histological effects of these formulation on corneal cells after 24 h of contact were also studied. The lowest absorption rate of cyclosporine A was found using olive oil with a percent absorption of 2.52 +/- 1.52% (259 +/- 171 micrograms/g cornea). The three formulations developed for this study, nanocapsules, poly(acrylic acid) polymeric gel and nanocapsules gel showed significantly better absorption of CsA than olive oil, with a mean percent absorption of 5.81 +/- 2.04% (621 +/- 218 micrograms/g cornea), 6.09 +/- 2.93% (651 +/- 313 micrograms cornea) and 7.92 +/- 2.55% (847 +/- 273 micrograms/g cornea) respectively. As we studied the penetration of cyclosporine A into the different layers of the cornea, we observed that for all formulations, CsA remained at the corneal surface and did not penetrate the whole cornea. The histological study showed that olive oil, nanocapsules and poly(acrylic acid) gel in aqueous/non-aqueous solvents show some modifications on the cornea, contrary to the nonocapsules gel which did not indicate any toxic effect. The nanocapsule gel, with the highest percent absorption along with its margin of safety on the cornea, seems to present a new promising drug delivery system for ocular administration.


Assuntos
Córnea/efeitos dos fármacos , Córnea/metabolismo , Ciclosporina/administração & dosagem , Ciclosporina/farmacocinética , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Resinas Acrílicas , Adsorção , Animais , Cápsulas , Bovinos , Córnea/patologia , Ciclosporina/toxicidade , Sistemas de Liberação de Medicamentos , Géis , Imunossupressores/toxicidade , Técnicas In Vitro , Azeite de Oliva , Soluções Oftálmicas , Óleos de Plantas
18.
Cancer Res ; 56(15): 3486-9, 1996 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-8758916

RESUMO

Breast cancer vasoactive intestinal peptide (VIP) receptors were characterized. Using in vitro autoradiographic techniques, 125I-labeled VIP bound with high affinity to breast biopsy sections. 125I-labeled VIP bound specifically to give breast cancer cell lines examined using receptor-binding techniques. Specific 125I-labeled VIP binding to MDA-MB-231 cells was inhibited with high affinity by VIP and pituitary adenylate cyclase-activating polypeptide (IC50, = 2 nM) and with moderate affinity by the VIP hybrid (IC50 = 0.5 microM). VIP elevated the cAMP in a dose-dependent manner, and VIP hybrid (10 microM) inhibited the increase in cAMP caused by VIP. Using Northern blot analysis, VIP (10 nM) stimulated c-fos and c-myc mRNA, and the increase caused by VIP was reversed by the VIP hybrid. The VIP hybrid inhibited breast cancer growth in vitro and in vivo using nude mice bearing breast cancer xenografts. These data suggest that the VIP hybrid is a breast cancer VIP receptor antagonist.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/ultraestrutura , Receptores de Peptídeo Intestinal Vasoativo/antagonistas & inibidores , Peptídeo Intestinal Vasoativo/farmacologia , Animais , Sítios de Ligação , Divisão Celular/efeitos dos fármacos , AMP Cíclico/metabolismo , Feminino , Genes fos , Humanos , Radioisótopos do Iodo/metabolismo , Cinética , Camundongos , Camundongos Endogâmicos BALB C , RNA Mensageiro/metabolismo , Receptores de Peptídeo Intestinal Vasoativo/metabolismo , Células Tumorais Cultivadas , Peptídeo Intestinal Vasoativo/metabolismo
19.
J Microencapsul ; 13(4): 473-80, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8808783

RESUMO

This study was undertaken to establish experimentally whether the intravitreal application of liposomally-entrapped ganciclovir could prolong intraocular therapeutic levels when it is compared to the intravitreal injection of a simple solution of the drug. New Zealand white rabbits were given an intravitreal injection of the drug solution and of liposome-encapsulated ganciclovir. The intravitreal clearance of ganciclovir was determined after a single injection of either the drug solution (200 micrograms/0.1 mL) or the liposomally-entrapped (with 41% load; 82 micrograms drug load and 118 micrograms free) ganciclovir. The ganciclovir vitreal concentrations were measured at various time intervals for a period up to 43 days using an HPLC method. The results of this study clearly demonstrated that prolonged intravitreal drug levels (above the mean inhibitory dose of cytomegalovirus of 1 microgram/mL) after administration of the liposome-entrapped ganciclovir and estimated to continue beyond 30-43 days. The injection of the 200 micrograms/0.1 mL of drug solution showed a mean vitreous concentration which was higher than the ID50 only for 55 h. The disappearance rate constant for the liposome-encapsulated injections was approximately 22 x slower than simple drug solution injections (controls). No evidence of retinal toxicity was found by clinical or light microscopy examination of the treated eyes.


Assuntos
Antivirais/administração & dosagem , Antivirais/farmacocinética , Ganciclovir/administração & dosagem , Ganciclovir/farmacocinética , Corpo Vítreo/metabolismo , Animais , Antivirais/análise , Cromatografia Líquida de Alta Pressão , Portadores de Fármacos , Ganciclovir/análise , Meia-Vida , Injeções , Lipossomos , Masculino , Microscopia Eletrônica , Tamanho da Partícula , Coelhos , Soluções
20.
J Microencapsul ; 12(5): 505-14, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8544094

RESUMO

In this study, the effect of the coat thickness of polyacrylate-polymethacrylate copolymer on the adsorption capacity of activated charcoal to methylene blue as a model marker was investigated by constructing both Langmuir and Freundlich isotherms. It was found that the coat thickness significantly affected the adsorption coefficient of the coated charcoal to methylene blue as is reflected by the attractive forces between the adsorbent and the adsorbate. This effect is understandable as the membrane will act as a barrier between the adsorbent and the adsorbate. The coat thickness also had some effect on the adsorption capacity of activated charcoal but not as much as it affected the adsorption coefficient. The data followed the Freundlich isotherm more closely than the Langmuir equation. The effect of the coat thickness on the adsorption of selected drugs of different molecular size was also investigated using theophylline, paracetamol, sodium phenobarbital, creatinine and vitamin B12 as model drugs. The results showed that the adsorption patterns of theophylline, paracetamol and sodium phenobarbital were more or less similar. The apparent coating thickness did not affect the extent of adsorption of these model drugs and there was little effect on the adsorption rate especially during the first 15 min. The adsorption of vitamin B12 and creatinine showed completely different patterns which are discussed in detail.


Assuntos
Carvão Vegetal , Hemoperfusão , Resinas Acrílicas , Adsorção , Cápsulas , Composição de Medicamentos , Géis , Azul de Metileno/química , Metilmetacrilato , Metilmetacrilatos , Peso Molecular , Ácidos Polimetacrílicos , Termodinâmica
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...