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61.
Riikka Laitinen Eero Suihko Kaisa Toukola Joakim Riikonen Kristiina Järvinen 《European journal of pharmaceutics and biopharmaceutics》2009,71(2):271-281
In this study, the dissolution rate of a poorly soluble drug, perphenazine (PPZ) was improved by a solid dispersion technique to permit its usage in intraoral formulations. Dissolution of PPZ (4 mg) in a small liquid volume (3 ml, pH 6.8) within one minute was set as the objective. PVP K30 and PEG 8000 were selected for carriers according to the solubility parameter approach and their 5/1, 1/5 and 1/20 mixtures with PPZ (PPZ/polymer w/w) were prepared by freeze-drying from 0.1 N HCl solutions. The dissolution rate of PPZ was improved with all drug/polymer mixture ratios compared to crystalline or micronized PPZ. A major dissolution rate improvement was seen with 1/5 PPZ/PEG formulation, i.e. PPZ was dissolved completely within one minute. SAXS, DSC and XRPD measurements indicated that solid solutions of amorphous PPZ in amorphous PVP or in partly amorphous PEG were formed. DSC and FTIR studies suggested that PPZ dihydrochloride salt was formed and hydrogen bonding was occurred between PPZ and the polymers. It was concluded that molecular mixing together with salt formation promoted the dissolution of PPZ, especially in the case of the 1/5 PPZ/PEG dispersion, making it a promising candidate for use in intraoral formulations. 相似文献
62.
63.
Mäki R Suihko E Rost S Heiskanen M Murtomaa M Lehto VP Ketolainen J 《Journal of pharmaceutical sciences》2007,96(2):438-447
In this study three model drugs (N-acetyl-D-glucosamine (NAG), anhydrous caffeine, and propranolol hydrochloride) were agglomerated with starch acetate (SA) by mixing the binary powders on a stainless steel (SS) plate. Agglomeration was induced by triboelectrification of the particles during mixing, and it was evaluated as a method to achieve controlled drug release rate. These agglomerates, mixed with different amounts of a disintegrant, were compressed into tablets whose dissolution characteristics were determined. Triboelectric measurements showed that when the drugs were in contact with SS, charges of the opposite polarity were generated to SA (+) and caffeine and NAG (-) promoting adhesion. Instead, propranolol HCl was charged with the same polarity as SA. SEM micrographs showed that smaller caffeine particles, in spite of their larger negative charge, agglomerated less efficiently with SA than larger NAG particles. This emphasizes the importance of particle size in the agglomeration process. Propranolol HCl did not form agglomerates with SA since their particle sizes and charges were identical. As a result, agglomeration of powders prior to tablet compression allows for modification and control of the release rate of the drugs from the SA matrix tablets as well as the tensile strength of the tablets. 相似文献
64.
In vitro release of heparin from silica xerogels. 总被引:3,自引:0,他引:3
M S Ahola E S S?ilynoja M H Raitavuo M M Vaahtio J I Salonen A U Yli-Urpo 《Biomaterials》2001,22(15):2163-2170
Heparin, a powerful anticoagulant used for the prophylaxis of both surgical and medical thrombosis, was incorporated into a silica xerogel matrix during polycondensation of organic silicate. The influence of various chemical sol-gel parameters (the properties of reaction precursors, catalyst and final moisture content of the gel and heparin concentration) was studied. The release of heparin from the gel was according to zero order during the dissolution period and the release rate of heparin was proportional to the drug load in the concentration range between 6.8 and 13.6 wt%. It was found that the catalyst used for the preparation of the gel, the final moisture content and the chemical modification of silica xerogel network have an influence on the release rate of heparin. The released heparin from all the different xerogels studied retained about 90% of its biological activity. 相似文献
65.
66.
Narvekar N Lakha F Critchley HO Glasier AF Williams AR Leminen R Heikinheimo O Kelly RW Baird DT 《Contraception》2007,75(4):271-280
BACKGROUND: We have previously shown that the antigestagen mifepristone is contraceptive when given in a daily dose of 5 mg, po. Epidemiological studies suggest that gestagen-only contraceptives may increase the risk of transmission of human immunodeficiency virus (HIV) due to effects on the vaginal defenses to infection. We investigate the effects of mifepristone on vaginal thickness, steroid receptor and natural antimicrobial content and pharmacokinetics of mifepristone. METHODS: In a pilot study, eight women were given mifepristone 5 mg/day for an average of 33 days. Ovarian function was assessed by measurement of estradiol and progesterone in blood and their metabolites in urine and by serial ultrasound of their ovaries. Vaginal biopsies were collected before (late proliferative) and after taking mifepristone. RESULTS: All subjects showed a similar pattern of descending serum concentrations of mifepristone. The elimination phase half-life was 18+/-5.1 h (mean+/-SD). Mean Cmax measured at 1 h was 641.7 nmol/L (range, 502-740 nmol/L). All eight women reported amenorrhea for the duration of treatment and seven of eight women showed biochemical and ultrasound evidence of anovulation. There was no significant change in vaginal thickness following treatment [342+/-40 microm pretreatment, 303+/-69 microm posttreatment (mean+/-SEM); p>.05]. Estrogen (ERalpha, ERbeta) and androgen receptor were expressed in both vaginal epithelium and subepithelial stroma, whereas progesterone receptor was expressed predominantly in the subepithelial stroma. There was no change in receptor content and distribution following mifepristone treatment. Natural antimicrobial mRNA [secretory leukocyte protease inhibitor, human beta defensins mRNA (HBD1, HBD2, HBD3, HBD5), granulysin and elafin] was extracted from the vaginal tissues, and the content was unaffected by mifepristone treatment. CONCLUSION: The absence of changes in vaginal thickness, steroid receptor and natural antimicrobial content and its distribution in this preliminary study suggests that in contrast to other estrogen-free contraceptives, mifepristone is unlikely to be associated with the increased risk of transmission of HIV and other sexually transmitted infections. 相似文献
67.
C Lamberg-Allardt M Ala-Houhala M Ahola M T Parviainen L R?s?nen J Visakorpi 《Annals of nutrition & metabolism》1986,30(4):267-272
3-,9- and 15-year-old children were studied in autumn in order to evaluate their serum 25-hydroxy-vitamin D (25-OH-D) concentration and their vitamin D intake. The 25-OH-D was significantly lower in the 15-year-old than in the other children, but it was satisfactory in all groups as compared to the 25-OH-D of healthy, young adults. The mean dietary vitamin D intake as well as the mean total vitamin D intake including supplements was low in all groups of children. With a vitamin D intake as low as in this study, every house-bound child would be at risk of vitamin D deficiency. 相似文献
68.
A.J. Ahola D. Gordin C. Forsblom P.-H. Groop 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2018,28(11):1166-1172
Background and aims
Increased arterial stiffness contributes to diabetic vascular complications. We identified dietary factors related to arterial stiffness in individuals with type 1 diabetes, a population with high risk of cardiovascular disease.Methods and results
Altogether, 612 participants (40% men, mean ± standard deviation age 45 ± 13 years) completed a validated diet questionnaire and underwent measurements of arterial stiffness. Of these, 470 additionally completed a food record. Exploratory factor analysis was applied to identify dietary patterns from the diet questionnaires, and nutrient intakes were calculated from food record entries. Arterial stiffness was measured by applanation tonometry. Of the seven dietary factors formed, the factor scores of “Full-fat cheese and eggs” and “Sweet” patterns were negatively associated with measures of arterial stiffness. In the multivariable macronutrient substitution models, favouring carbohydrates over fats was associated with higher aortic mean arterial pressure and aortic pulse wave velocity. When carbohydrates were consumed in place of proteins, higher aortic pulse pressure, aortic mean arterial pressure, and augmentation index were recorded. Replacing energy from alcohol with proteins, was associated with lower aortic pulse pressure, aortic mean arterial pressure, and augmentation index. Relative distributions of dietary fatty acids were neutral with respect to the measures of arterial stiffness.Conclusion
The macronutrient distribution of the diet is likely to affect the resilience of the arteries. Our observations suggest that reducing energy intake from carbohydrates and alcohol may be beneficial. These observations, especially those dealing with dietary patterns, need to be confirmed in a longitudinal study. 相似文献69.
70.
Objectives We examined the rate of functional change (using performance measures and a self-report questionnaire) during interdisciplinary occupational rehabilitation in workers?? compensation claimants with a variety of musculoskeletal conditions. We also estimated the rate of improvement that could be considered clinically important and examined factors associated with rate of functional improvement. Methods A prospective cohort design was used, with data collected before and after claimants participated in an interdisciplinary occupational rehabilitation program. A consecutive sample was formed of claimants admitted between July 2005 and June 2007. Measures included performance-based functional measures (functional capacity evaluation, FCE) and a self-report questionnaire (pain disability index, PDI). Results The sample included 582 compensation claimants with a variety of musculoskeletal conditions. The majority of claimants experienced functional improvement during rehabilitation. Claimants with the outcome status ??Return-to-Work Pre-accident?? had the highest rate of functional change (up to 5?kg/week on floor to waist lifting, ~7 points/week on the PDI). Conclusion The clinically important rate of functional change appears to be 5?kg/week on FCE floor-to-waist lifting and 7 points/week on the PDI (scored out of 100). Rate of functional change appears to be multifactorial, with a variety of physical, demographic, clinical, and environmental factors explaining rate of change. 相似文献