Changes in health-related quality of life (EQ-5D) dimensions associated with community-based musculoskeletal physiotherapy: a multi-centre analysis.

PURPOSE: To determine the changes in each of the five dimensions of the EuroQol 5-dimension index associated with community-based physiotherapy. METHODS: Four thousand one hundred and thirty-six patients that received community-based musculoskeletal physiotherapy across five NHS centres completed the EQ-5D on entry into the service and upon discharge. Patients were categorised on symptom location and response to treatment based on their EQ-5D index improving by at least 0.1 ("EQ-5D responders"). For each symptom location, and for responders and non-responders to treatment, the mean (± SD) were calculated for each dimension pre- and post-treatment as well as the size of effect. RESULTS: The mobility dimension improved (p < 0.05) in all symptom locations for EQ-5D responders (d = 0.26-1.58) and in ankle, knee, hip and lumbar symptoms for EQ-5D non-responders (d = 0.17-0.45). The self-care dimension improved (p < 0.05) in all symptom locations for EQ-5D responders (d = 0.49-1.16). The usual activities dimension improved (p < 0.05) across all symptom locations for EQ-5D responders (d = 1.00-1.75) and EQ-5D non-responders (d = 0.14-0.60). Despite the pain/discomfort dimension improving (p < 0.05) across all symptom locations for both EQ-5D responders (d = 1.07-1.43) and EQ-5D non-responders (d = 0.29-0.66), the anxiety/depression dimension improved (p < 0.05) from higher starting levels in EQ-5D responders (d = 0.76-1.05) with no change seen for EQ-5D non-responders (d = - 0.16 to 0.06). CONCLUSIONS: Clinicians should not assume that a patient presenting with pain but expressing high anxiety/depression is unlikely to respond to treatment, as they may show the best HRQoL outcomes. For patients presenting with pain/discomfort and low levels of anxiety/depression, the EQ-5D index is perhaps not a suitable tool for sole use in patient management and service evaluation.

Thymopoiesis following HSCT; a retrospective review comparing interventions for aGVHD in a pediatric cohort.

Acute graft-versus-host disease (aGVHD) complicates allogeneic hematopoietic stem cell transplantation (HSCT), and is treated with topical and/or systemic corticosteroids. Systemic corticosteroids and aGVHD damage thymic tissue. We compared thymopoietic effect of topical steroid therapy, corticosteroids and extracorporeal photopheresis (ECP) in 102 pediatric allogeneic HSCT patients. We categorized patients into 4 groups: - no aGVHD, aGVHD treated with topical or systemic steroid, or ECP. Naïve CD4+CD45RA+CD27+ T-lymphocyte values at 3, 6, 9, 12months post-HSCT were recorded: for ECP patients, values were recorded at 3, 6, 9, 12months during ECP. Differences were compared using the Kruskal-Wallis test. 41 patients had no aGVHD, 23 had aGVHD treated topically or systemically (25), 13 received ECP. Rate of thymopoiesis was significantly different between all groups at all time-points post-transplant (p=0.002, p<0.001, p<0.001, p=0.001 respectively). Even mild aGVHD impairs thymopoiesis. Worst recovery was in ECP patients. Earlier institution of ECP may speed thymic recovery.

Associations between community-based physiotherapy for musculoskeletal injury and health related quality of life (EQ-5D): a multi-centre retrospective analysis.

BACKGROUND: Community-based musculoskeletal physiotherapy is used to improve function and health related quality of life (HRQoL). The purpose of this retrospective, multi-centre observational study was to determine the association between community-based physiotherapy management for musculoskeletal disorders and changes in HRQoL. METHODS: Four thousand one hundred twelve patients' data were included in the study. Patients were included if they received a single period of treatment for a musculoskeletal injury or disorder. Patients were only included if they were being treated for a single morbidity. Patients received standard physiotherapy appropriate to their specific disorder, which could include health education/advice, exercise therapy, manual therapy, taping, soft tissue techniques, electrotherapy and/or acupuncture. Health related quality of life was assessed using the EQ-5D index. RESULTS: EQ-5D improved by 0.203 across all patients (d = 1.10). When grouped by anatomical site of symptom, the largest increases in EQ-5D was in foot pain (0.233; d = 1.29) and lumbar pain (0.231; d = 1.13). Improvements in EQ-5D greater than the minimum clinically important difference (MCID) were seen in 68.4% of all patients. The highest proportion of patients with positive responses to treatment were in ankle pain (74.2%) and thoracic pain (73.4%). The hand (40.5%), elbow (34.7%), and hip (33.9%) showed the greatest proportion of patients that did not respond to treatment. CONCLUSIONS: Community-based musculoskeletal physiotherapy is associated with improved health related quality of life. A randomised controlled trial is needed to determine any causal relationship between community-based physiotherapy and health related quality of life improvements.

Antioxidant, analgesic and anti-inflammatory effects of lavender essential oil.

Several studies have investigated the antinociceptive, immunomodulatory and anti-inflammatory properties of compounds found in the lavender essential oil (LEO), however to date, there is still lack of substantial data. The objective of this study was to assess the antioxidant, anti-inflammatory and antinociceptive effects of lavender essential oil. The 1,1-diphenyl-2-picrylhydrazyl radical decolorization assay was used for antioxidant activity evaluation. The anti-inflammatory activity was tested using two models of acute inflammation: carrageenan-induced pleurisy and croton oil-induced ear edema. The antinociceptive activity was tested using the pain model induced by formalin. LEO has antioxidant activity, which is dose-dependent response. The inflammatory response evoked by carrageenan and by croton oil was reduced through the pre-treatment of animals with LEO. In the pleurisy model, the drug used as positive control, dexamethasone, was more efficacious. However, in the ear swelling, the antiedematogenic effect of the oil was similar to that observed for dexamethasone. In the formalin test, LEO consistently inhibited spontaneous nociception and presented a similar effect to that of tramadol. The results of this study reveal (in vivo) the analgesic and anti-inflammatory activities of LEO and demonstrates its important therapeutic potential.

Phenolic enriched extract of Baccharis trimera presents anti-inflammatory and antioxidant activities.

Baccharis trimera is a plant popularly used as a tea and to treat gastrointestinal diseases and inflammatory processes as well. The total phenolic content was determined and the antioxidant and anti-inflammatory activities of six extracts (dichloromethane, ethyl acetate, butanol, aqueous, saponin and phenolic) from B. trimera were evaluated. Using carrageenan-induced pleurisy as a model of acute inflammation, the phenolic extract at 15 mg/kg decreased significantly the analyzed parameters when compared to the carrageenan group ( p < 0.05), thus showing potential anti-inflammatory activity. The total phenolic content and antioxidant activity were evaluated by the Folin-Ciocalteau and DPPH methods, respectively. Phenolic and ethyl acetate extracts presented higher antioxidant activity ( p < 0.05) than ascorbic acid. The phenolic extract also showed the highest antioxidant potential in relation to the other extracts, thus suggesting that the antioxidant and anti-inflammatory activities were due to the presence of phenolic compounds.

The effect of altering the 20:5n-3 and 22:6n-3 content of a meal on the postprandial incorporation of n-3 polyunsaturated fatty acids into plasma triacylglycerol and non-esterified fatty acids in humans.

Previous studies suggest that consuming meals containing large amounts of fish oil is associated with selective postprandial incorporation of 20:5n-3 and 22:6n-3 into plasma non-esterified fatty acids (NEFA). We investigated the effect of consuming meals containing different amounts of 20:5n-3 and 22:6n-3 comparable to dietary habits of western populations on the postprandial incorporation of 18:3n-3, 20:5n-3 and 22:6n-3 into plasma triacylglycerol (TAG) and NEFA over 6h in middle aged subjects. 20:5n-3 incorporation into plasma TAG was greater than 22:6n-3 irrespective of the test meal. Conversely, 22:6n-3 incorporation into plasma NEFA was greater than 20:5n-3, irrespective of the test meal. There was no effect of the amount of 20:5n-3+22:6n-3 in the test meal on the 18:3n-3 incorporation into plasma TAG or NEFA. These findings suggest differential metabolism of 20:5n-3 and 22:6n-3 in the postprandial period when consumed in amounts typical of western dietary habits.

Ascorbic acid deficiency, iron overload and alcohol abuse underlie the severe osteoporosis in black African patients with hip fractures--a bone histomorphometric study.

Osteoporosis and femoral neck fractures (FNF) are uncommon in black Africans although osteoporosis accompanying iron overload (from traditional beer brewed in iron containers) associated with ascorbic acid deficiency (oxidative catabolism by iron) has been described from sub-Saharan Africa. This study describes histomorphometric findings of iliac crest bone biopsies and serum biochemical markers of iron overload and of alcohol abuse and ascorbic acid levels in 50 black patients with FNFs (29 M, 21 F), age 62 years (40-95) years (median [min-max]), and in age- and gender-matched black controls. We found evidence of iron overload in 88% of patients and elevated markers of alcohol abuse in 72%. Significant correlations between markers of iron overload and of alcohol abuse reflect a close association between the two toxins. Patients had higher levels of iron markers, i.e., siderin deposits in bone marrow (P < 0.0001), chemical non-heme bone iron (P = 0.012), and serum ferritin (P = 0.017) than controls did. Leukocyte ascorbic acid levels were lower (P = 0.0008) than in controls. The alcohol marker mean red blood cell volume was elevated (P = 0.002) but not liver enzymes or uric acid. Bone volume, trabecular thickness, and trabecular number were lower, and trabecular separation was greater in patients than in controls, all at P < 0.0005; volume, surface, and thickness of osteoid were lower and eroded surface was greater, all at P < 0.0001. There was no osteomalacia. Ascorbic acid deficiency accounted significantly for decrease in bone volume and trabecular number, and increase in trabecular separation, osteoid surface, and eroded surface; iron overload accounted for a reduction in mineral apposition rate. Alcohol markers correlated negatively with osteoblast surface and positively with eroded surface. Relative to reported data in white FNF patients, the osteoporosis was more severe, showed lower osteoid variables and greater eroded surface; FNFs occurred 12 years earlier and were more common among men. We conclude that the osteoporosis underlying FNFs in black Africans is severe, with marked uncoupling of resorption and formation in favor of resorption. All three factors--ascorbic acid deficiency, iron overload, and alcohol abuse--contributed to the osteoporosis, in that order.

Effects of chemotherapy on bone metabolism and skeletal growth.

In recent years there has been a significant increase in both acute and chronic toxicity associated with the more successful but now highly intensive chemotherapy (CT) regimens used to treat childhood cancers. The incidence of childhood cancers coincides with periods of rapid skeletal development. Consequently, short stature and osteoporosis are important long-term effects in adult survivors. Clinical data indicate that the effects of CT, including glucocorticoids, on final height are due to direct effects of these drugs on the skeleton. The multiple modes of action of CT drugs suggest a complex and diverse influence on chondrocytes, extracellular matrix and bone cells. However, only limited data demonstrate these direct effects on the proliferative capacity of growth plate chondrocytes and on key steps of endochondral ossification, the multistep process that determines rate and extent of long bone growth. Endochondral ossification requires coordinated maturation, proliferation and differentiation of growth plate chondrocytes leading to hypertrophic cells which eventually undergo apoptosis to leave a cartilaginous scaffold that is mineralized prior to the laying down of new bone. Disruption of the physiological cellular activity of growth plate chondrocytes and/or bone cells result in skeletal growth disturbances. Thus, CT drugs which disrupt normal cell division may manifest their effects on the growth plate as either a reduction in cell number and/or the loss of functional integrity of extracellular matrix. Histological and cell kinetic studies, using in vivo and in vitro models of long bone growth, are essential to increase our understanding of the cellular mechanisms involved and to finally determine how the individual growth potential might be maintained during treatment for childhood cancers.

Platinum agents in the treatment of osteosarcoma: efficacy of cisplatin vs. carboplatin in human osteosarcoma cell lines.

BACKGROUND: Cisplatin (cDDP), when used either alone or, more often, in combination with other agents, especially adriamycin, achieves a high response rate in osteosarcoma. Its use, however, is limited by severe nephro- and neuro-toxicity. Second generation platinum compounds, most notably carboplatin (CBDCA), have been developed in order to attempt to reduce these dose-limiting toxicities, and thus improve the therapeutic ratio. Studies evaluating the role of combination CT containing CBDCA vs. cDDP have demonstrated differing results depending on the tumor type tested and its role in the treatment of osteosarcoma has yet to be clarified. PROCEDURE: In this study, we compared the in vitro anti-tumor activity of cDDP and CBDCA in a panel of three human osteosarcoma cell lines (HOS, MG63, and U2OS). RESULTS: cDDP and CBDCA (0-20 micromol) showed marked variation in cytotoxicity among the three cell lines. EC(50) values for CBDCA in HOS and MG63 cells were approximately two-fold higher than for cDDP and the ratio of AUC(CBDCA) to AUC(cDDP) varied from 1.8 in the HOS cell line to 2.3 in the MG63 cell line. Exposure of MG63 and HOS cells to either cDDP or CBDCA (1.67 and 13.5 micromol) caused a G2/M cell cycle arrest by 24 hr. Also evident was a sub G1 peak indicative of cell death by apoptosis. U2OS cells were relatively resistant to the cytotoxic effects of both drugs, although a cell cycle arrest in response to DNA damage was observed. This suggests that unlike MG63 and HOS cells, U2OS cells have either a more efficient repair pathway for platinum-induced DNA damage or are able to evade apoptosis. Examination of apoptotic events and cellular recovery demonstrated that both an 8-16-fold higher concentration and longer treatment period for CBDCA compared with cDDP was required to produce equivalent cell death and a loss of the ability of single cell clones to form colonies in both the HOS and MG63, but not the U2OS cell line. CONCLUSIONS: Our findings suggest that CBDCA at a two- to four-fold higher concentration than cDDP has potential therapeutic activity in platinum sensitive osteosarcomas, particularly when cDDP cytotoxicity compromises therapeutic efficacy.

Dexamethasone inhibits and thyroid hormone promotes differentiation of mouse chondrogenic ATDC5 cells.

The effects of glucocorticoid (GC) excess, thyrotoxicosis, and hypothyroidism on linear growth indicate that growth plate chondrocytes are exquisitely sensitive to GC and thyroid hormone (T(3)). Murine ATDC5 cells undergo chondrogenesis in vitro and were used to evaluate the effects of dexamethasone (Dex) and T(3) on cell proliferation and differentiation. Immature and differentiated ATDC5 cells expressed glucocorticoid and T(3)-receptor mRNAs. Cells proliferated and organized into cartilage-like nodules after 7 days. Chondrocyte maturation progressed over 9-40 days, with increasing alkaline phosphatase (ALP) activity, secretion of an Alcian blue-positive matrix, and mineralization of cartilage-like nodules. Dex reduced cell number over the 40 day period, causing inhibition of ALP activity and matrix production with failure of mineralization. Following withdrawal of Dex, chondrocytes proliferated and re-entered the differentiation and mineralization program, indicating that GC inhibition of chondrogenesis is reversible. In contrast, T(3) reduced cell proliferation, but induced ALP activity and increased matrix secretion earlier than in control cultures. Thus, GCs and T(3) regulate growth plate chondrocyte differentiation by distinct mechanisms. GCs arrest cell proliferation, differentiation, and cartilage mineralization and maintain chondrocyte precursors in a state of quiescence with the capacity to re-enter chondrogenesis. T(3) inhibits cell proliferation but accelerates differentiation to stimulate chondrogenesis.

The caspase 8 inhibitor c-FLIP(L) modulates T-cell receptor-induced proliferation but not activation-induced cell death of lymphocytes.

The caspase 8 inhibitor c-FLIP(L) can act in vitro as a molecular switch between cell death and growth signals transmitted by the death receptor Fas (CD95). To elucidate its function in vivo, transgenic mice were generated that overexpress c-FLIP(L) in the T-cell compartment (c-FLIP(L) Tg mice). As anticipated, FasL-induced apoptosis was inhibited in T cells from the c-FLIP(L) Tg mice. In contrast, activation-induced cell death of T cells in c-FLIP(L) Tg mice was unaffected, suggesting that this deletion process can proceed in the absence of active caspase 8. Accordingly, c-FLIP(L) Tg mice differed from Fas-deficient mice by showing no accumulation of B220(+) CD4(-) CD8(-) T cells. However, stimulation of T lymphocytes with suboptimal doses of anti-CD3 or antigen revealed increased proliferative responses in T cells from c-FLIP(L) Tg mice. Thus, a major role of c-FLIP(L) in vivo is the modulation of T-cell proliferation by decreasing the T-cell receptor signaling threshold.

Thyroid status affects number and localization of thyroid hormone receptor expressing mast cells in bone marrow.

Thyroid hormone (T(3)) plays a key role in endochondral ossification. The process relies on the coordinated synthesis and degradation of cartilage matrix and is disrupted in juvenile hypothyroidism, leading to abnormal skeletal development. Mast cells synthesize and store matrix-degrading enzymes. We examined whether thyroid status influences skeletal mast cell distribution in growing rats to determine whether they might modulate the actions of T(3) in bone. Tibiae were collected for histological, histochemical, immunohistochemical, and immunofluorescence analysis. Mast cells were increased throughout the bone marrow in hypothyroid rats compared with euthyroid, thyrotoxic, and hypothyroid-thyroxine replaced animals. Large numbers were present in metaphyseal marrow adjacent to the growth plate in hypothyroid animals and cells were distributed evenly throughout the marrow. Very few mast cells were present in metaphyseal marrow in other groups, but their numbers increased with increasing distance from the growth plate. T(3) receptor alpha1 (TRalpha1) was expressed in the nucleus and cytoplasm of skeletal mast cells, whereas TRalpha2 and TRbeta1 were restricted to the cytoplasm. Localization of TRs was not affected by altered thyroid status. Thus, disrupted endochondral ossification in hypothyroidism may be mediated in part by skeletal mast cells, which express TR proteins and may function as T(3) target cells.

Susceptibility of the Bacteroides fragilis group to newer quinolones and other standard anti-anaerobic agents.

The susceptibilities of 200 clinical isolates of the Bacteroides fragilis group to four quinolones (moxifloxacin, clinafloxacin, trovafloxacin and ciprofloxacin) were determined, as well as to cefoxitin, clindamycin, metronidazole, imipenem and ticarcillin-clavulanic acid. The results for the latter five agents were compared with those of a study on 200 isolates done 6 years previously. Clinafloxacin and trovafloxacin were the most active agents tested with MIC90s lower than all other antimicrobials except imipenem. Susceptibility rates for imipenem, ticarcillin- clavulanic and metronidazole continue to be high, although resistant strains are emerging. For ticarcillin-clavulanic acid and metronidazole, MIC90s increased four- to eight-fold for the B. fragilis species between the two study periods.

Glucocorticoids, thyroid hormone and growth hormone interactions: implications for the growth plate.

Linear growth occurs during childhood and results from endochondral ossification in the growth plate. Prepubertal growth is primarily regulated by growth hormone (GH) and insulin-like growth factor (IGF)-I, with important contributions from glucocorticoids (GC) and thyroid hormone (T(3)). The somatomedin hypothesis proposed that GH stimulates hepatic IGF-I production, which then regulates growth via IGF-I receptor expressing chondrocytes in an endocrine fashion. Recent studies indicate that locally acting IGF-I is a key determinant of endochondral ossification and that GH, GC and T(3) regulate expression of IGF-I and its receptor in the growth plate directly. Analysis of hormone imbalance during childhood and studies of genetically modified mice provide support for an important GH and IGF-I autocrine/paracrine pathway and for direct effects of GC and T(3) during endochondral ossification. Thus, the epiphyseal growth plate is a key site for convergent hormone action that mediates the control of linear growth.

Thyroid hormones regulate hypertrophic chondrocyte differentiation and expression of parathyroid hormone-related peptide and its receptor during endochondral bone formation.

Hypothyroidism in children causes developmental abnormalities in bone and growth arrest, while thyrotoxicosis accelerates growth rate and advances bone age. To determine the effects of thyroid hormones on endochondral bone formation, we examined epiphyseal growth plates in control, hypothyroid, thyrotoxic, and hypothyroid-thyroxine (hypo-T4)-treated rats. Hypothyroid growth plates were grossly disorganized, contained an abnormal matrix rich in heparan sulfate, and hypertrophic chondrocyte differentiation failed to progress. These effects correlated with the absence of collagen X expression and increased parathyroid hormone-related protein (PTHrP) messenger RNA (mRNA) expression. In thyrotoxic growth plates, histology essentially was normal but PTHrP receptor (PTHrP-R) mRNA was undetectable. PTHrP is a potent inhibitor of hypertrophic chondrocyte differentiation that acts in a negative feedback loop with the secreted factor Indian hedgehog (Ihh) to regulate endochondral bone formation. Thyroid hormone receptor alpha1(TRalpha1), TRalpha2, and TRbeta1 proteins were localized to reserve zone progenitor cells and proliferating chondrocytes in euthyroid rat cartilage; regions in which PTHrP and PTHrP-R expression were affected by thyroid status. Thus, dysregulated Ihh/PTHrP feedback loop activity may be a key mechanism that underlies growth disorders in childhood thyroid disease.

Thyroid hormone acts directly on growth plate chondrocytes to promote hypertrophic differentiation and inhibit clonal expansion and cell proliferation.

T3 is an important regulator of endochondral bone formation in epiphyseal growth plates. Growth arrest in juvenile hypothyroidism results from disorganization of growth plate chondrocytes and their failure to undergo hypertrophic differentiation, but it is unclear how T3 acts directly on chondrocytes or whether its actions involve other pathways. To address this issue, we investigated whether thyroid hormone receptors (TR) were localized to discrete regions of the unfused epiphysis by immunohistochemistry performed in tibial growth plates from 21-day-old rats and examined the effects of T3 on growth plate chondrocytes in agarose suspension cultures in vitro. TRalpha1, -alpha2, and -beta1 were expressed in reserve and proliferating zone chondrocytes, but not in hypertrophic cells, suggesting that progenitor cells and immature chondrocytes are the major T3 target cells in the growth plate. Chondrocytes in suspension culture expressed TRalpha1, -alpha2, and -beta1 messenger RNAs and matured by an ordered process of clonal expansion, colony formation, and terminal hypertrophic differentiation. Clonal expansion and proliferation of chondrocytes were inhibited by T3, which also induced alkaline phosphatase activity, expression of collagen X messenger RNA, and secretion of an alcian blue-positive matrix as early as 7 days after hormone stimulation. Thus, T3 inhibited chondrocyte clonal expansion and cell proliferation while simultaneously promoting hypertrophic chondrocyte differentiation. These data indicate that thyroid hormones concurrently and reciprocally regulate chondrocyte cell growth and differentiation in the endochondral growth plate.

An investigation into the release of cefuroxime axetil from taste-masked stearic acid microspheres. III. The use of DSC and HSDSC as means of characterising the interaction of the microspheres with buffered media.

Stearic acid coated cefuroxime axetil (SACA) microspheres have been studied using differential scanning calorimetry (DSC) and high sensitivity DSC (HSDSC) in order to examine the interaction between the spheres and a range of buffer systems, with a view to further enhance the understanding of the mechanism of drug release developed in earlier studies [Robson et al., 1999, 2000]. DSC studies indicated that after immersion in Sorensens modified phosphate buffer (SMPB) pH 5.9 followed by washing and drying, no change in the thermal properties of the spheres was detected up to 60 min of immersion, with a single endotherm noted at circa 56 degrees C, that corresponded to the melting of the stearic acid used in this study; similar results were obtained for systems immersed in distilled water. After immersion in SMPB pH 7.0 and 8.0, however, a second peak was noted at approximately 67 degrees C that increased in magnitude relative to the lower temperature endotherm with increasing exposure time to the medium. Spheres that had not been previously washed prior to drying showed complete conversion to the higher temperature endotherm for these two buffers. Systems which had been exposed to a range of pH 7.0 buffers (citrate-phosphate buffer (CPB), phosphate buffer mixed (PBM), boric acid buffer (BAB)) were then examined. Only the CPB systems showed evidence for conversion to the higher melting form. PBM systems to which further sodium had been added were then examined. A maximum conversion was found at 0.05 M sodium, which was in agreement with the maximum in release rate found in a previous study [Robson et al., 2000]. HSDSC was then used to examine systems that were immersed in the buffer. For SMPB, pH 5.9 and distilled water, only the endotherm corresponding to the stearic acid melting was seen. However, for SMPB pH 7.0 and 8.0, three peaks were seen, two corresponding to those seen for the DSC studies and a further lower temperature peak at circa 44 degrees C. Studies on PBM systems to which additional sodium had been added showed small levels of conversion to the higher temperature form at higher sodium contents. The data was discussed in terms of the correlation with earlier dissolution studies on the same systems [Robson et al., 1999; 2000].

An investigation into the release of cefuroxime axetil from taste-masked stearic acid microspheres. II. The effects of buffer composition on drug release.

The influence of buffer composition on the release of cefuroxime axetil from stearic acid microspheres has been investigated, with particular emphasis on establishing the relationship between buffer composition and release at a single pH value. Studies of drug dissolution and release from spheres in pH 7.0 citrate phosphate buffer (CPB), boric acid buffer (BAB), phosphate buffer mixed (PBM) and Sorensens modified phosphate buffer (SMPB) indicated marked differences in release profile from the spheres, with an approximate rank order of SMPB > CPB approximately BAB > PBM. The role of added sodium was then investigated by examining the release profiles in SMPB and PBM to which sodium ions had been added. Increases in the sodium content from approximately 0.11 to 0.2 M were found to decrease the release rate for the SMPB, while increases from 0.007 to 1.0 M sodium in PBM resulted in a maximum release being seen for the systems containing 0.05 M sodium. Studies on surface disintegration, using scanning electron microscopy (SEM) and sodium uptake using flame emission spectroscopy, indicated an interrelationship between medium composition, disintegration and release. The data are discussed in terms of the possible mechanisms associated with drug release from these spheres.

An investigation into the release of cefuroxime axetil from taste-masked stearic acid microspheres. Part 1: the influence of the dissolution medium on the drug release profile and the physical integrity of the microspheres.

The dissolution properties of stearic acid-coated cefuroxime axetil (SACA) systems have been studied with a view to investigating the effects of the dissolution medium on both the release rate and the physical integrity of the microspheres. The release from the spheres was found to be highly dependent on the media used, with systems in distilled water (pH 6.8) and pH 5.9 Sorensens modified buffer showing a relatively slow release which exhibited linearity with the square root of time, implying a diffusion process. The rate of release from systems in pH 7.0 and 8.0 buffer was considerably faster and did not follow simple diffusion kinetics. Examination of the microspheres after immersion in the various media indicated a change in the integrity of the spheres in those media which showed the most rapid release. This was particularly marked when the systems were dried in buffer, with disintegration seen in the higher pH systems. It is suggested that the release of the drug is dependent both on diffusion through the intact microspheres and changes in the physical integrity of the spheres as a result of a reaction with the surrounding medium.