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Budesonide inhalation suspension: a review of its use in infants, children and adults with inflammatory respiratory disorders.

Budesonide, a topically active corticosteroid, has a broad spectrum of clinically significant local anti-inflammatory effects in patients with inflammatory lung diseases including persistent asthma. In infants and young children with persistent asthma, day- and night-time symptom scores, and the number of days in which beta2-agonist bronchodilators were required, were significantly lower during randomised, double-blind treatment with budesonide inhalation suspension 0.5 to 2 mg/day than placebo in 3 multicentre trials. Significantly fewer children discontinued therapy with budesonide inhalation suspension than with placebo because of worsening asthma symptoms in a study that included children who were receiving inhaled corticosteroids at baseline. Recent evidence indicates that budesonide inhalation suspension is significantly more effective than nebulised sodium cromoglycate in improving control of asthma in young children with persistent asthma. At a dosage of 2 mg/day, budesonide inhalation suspension significantly reduced the number of asthma exacerbations and requirements for systemic corticosteroids in preschool children with severe persistent asthma. In children with acute asthma or wheezing, the preparation was as effective as, or more effective than oral prednisolone in improving symptoms. In children with croup, single 2 or 4mg dosages of budesonide inhalation suspension were significantly more effective than placebo and as effective as oral dexamethasone 0.6 mg/kg or nebulised L-epinephrine (adrenaline) 4mg in alleviating croup symptoms and preventing or reducing the duration of hospitalisation. Early initiation of therapy with budesonide inhalation suspension 1 mg/day appears to reduce the need for mechanical ventilation and decrease overall corticosteroid usage in preterm very low birthweight infants at risk for chronic lung disease. In adults with persistent asthma, budesonide inhalation suspension < or =8 mg/day has been compared with inhaled budesonide 1.6 mg/day and fluticasone propionate 2 mg/day administered by metered dose inhaler. Greater improvements in asthma control occurred in patients during treatment with budesonide inhalation suspension than with budesonide via metered dose inhaler, whereas fluticasone propionate produced greater increases in morning peak expiratory flow rates than nebulised budesonide. Several small studies suggest that the preparation has an oral corticosteroid-sparing effect in adults with persistent asthma and that it may be as effective as oral corticosteroids during acute exacerbations of asthma or chronic obstructive pulmonary disease. The frequency of adverse events was similar in children receiving budesonide inhalation suspension 0.25 to 2 mg/day or placebo in 12-week studies. During treatment with budesonide inhalation suspension 0.5 to 1 mg/day in 3 nonblind 52-week studies, growth velocity in children was generally unaffected; however, a small but statistically significant decrease in growth velocity was detected in children who were not using inhaled corticosteroids prior to the introduction of budesonide inhalation suspension. Hypothalamic-pituitary-adrenal axis function was not affected by short (12 weeks) or long (52 weeks) term treatment with nebulised budesonide. In conclusion, budesonide inhalation suspension is the most widely available nebulised corticosteroid, and in the US is the only inhaled corticosteroid indicated in children aged > or =1 year with persistent asthma. The preparation is suitable for use in infants, children and adults with persistent asthma and in infants and children with croup.

Administration, Inhalation↗

Flow properties of hemolysate-loaded liposome suspensions.

Sheep hemolysate-loaded liposomes were prepared by a modified interfacial deposition technique. The mean diameter of the liposomes was estimated to be about 310 nm. Sheep hemolysate-loaded liposomes were called artificial red blood cells (ARBC). The flow properties of the ARBC suspension (pH 7.4) were measured with a concentric cylinder-type rorational viscometer at low shear rates and were compared with those of sheep red blood cell (SRBC) suspension (pH 7.4). It was revealed that the flow type of the ARBC suspension (pH 7.4) was of pseudoplastic as in the case of SRBC suspension (pH 7.4). The relative viscosity of the ARBC suspension as a function of particle concentration in the medium was linear and fitted fairly well with the Einstein equation. However, the relative viscosity of SRBC suspension was increased more gradually with increasing particle concentration, and was well presented by the Brinkman equation as a function of particle concentration for concentrated suspensions. It was suggested that this would be due to the difference in particle-particle interaction between the two types of suspensions. The flow properties of the mixed suspensions of the ARBC and SRBC in the suspending medium (pH 7.4) with and without dextran were measured. It was revealed that the relative viscosity of the mixed suspension is reduced with increasing mixing ratio of the ARBC in the suspension, suggesting that the flow properties of the mixed suspension of the ARBC and SRBC are dependent on the ARBC rather than dextran.

Animals↗

Multi-omics reveal molecular changes during suspension adaptation of HEK293 cells.

Human embryonic kidney 293 (HEK293) cells have been successfully adapted from adherent to suspension culture and widely applied in both scientific research and the pharmaceutical industry. Although some studies investigated the variances between established adherent and suspension HEK293 cells of different strains, specific alterations in the cells during this consecutive process of suspension adaptation and possible factors driving this process have not been well described. Here, we adapted adherent HEK293 to suspension with desirable cell growth and high productivity for recombinant adenoviral vectors, and cells at several stages throughout the process were characterized. Slower cell growth, lower glucose uptake, increased lactate production, and weaker cell-surface adhesion were observed in suspension cells compared to their adherent counterparts. We further performed transcriptomics, proteomics, and metabolomics analysis to identify key cellular switches. A total of 2476 differentially expressed genes were found, including 1218 upregulated and 1258 downregulated genes in suspension cells. A similar and correlated pattern was observed in the proteomic study, and 702 differentially expressed metabolites were identified by untargeted metabolomics. In light of enrichment analysis, we summarized that HEK293 adherent cells survived and adapted to suspension culture via structural remodeling, metabolic shift and stress resistance. Our results provide a molecular enlightenment for suspension adaptation and potential directions for rational modification of HEK293 cell lines for future use. KEY POINTS: &#x2022; Suspension adaptation reduced adhesion and reshaped the HEK293 cytoskeleton. &#x2022; Multi-omics revealed metabolic rewiring and enhanced stress resistance. &#x2022; An optimized suspension line outperformed an internal HEK293 suspension reference.

Humans↗

Stability of rifampin in two suspensions at room temperature.

The objective of our study was to determine the stability of rifampin (rifampcin) in two extemporaneously prepared suspensions at room temperature. Two suspensions were prepared in syrup by using intravenous rifampin (A) or rifampin capsules (B). Each suspension was stored in five plastic prescription bottles. During the first week, the mean measured concentrations of rifampin were nearly 100% of initial concentration in suspension A, but were 77-83% of the expected (labelled) concentration in suspension B. The maximum concentrations of rifampin were observed immediately after preparation of suspension A, but not until 14 days in suspension B. On day 56, the mean concentration of rifampin was about 95% of initial concentration in suspension A, and close to 90% of the labelled potency (10 mg/ml) in suspension B. Rifampin was found to be chemically stable in each suspension for 56 days at room temperature. Suspensions prepared from the capsules may be non-homogeneous and lead to unsatisfactory dosing.

Capsules↗

Recovery of phenytoin suspension after in vitro administration through percutaneous endoscopic gastrostomy Pezzer catheters.

Various methods of administering phenytoin suspension through a percutaneous endoscopic gastrostomy (PEG) Pezzer catheter were evaluated in vitro to determine which method resulted in the most complete recovery of phenytoin. To determine the effect of temperature on phenytoin recovery, 12 mL of phenytoin suspension (Dilantin-125, 125 mg/5 mL) was administered through three separate 35.5-cm 20 French latex PEG Pezzer catheters under each of three temperature conditions (suspension 11.8 degrees C and catheter 22 degrees C, suspension and catheter 22 degrees C, and suspension 22 degrees C and catheter 37 degrees C). To determine the effect of the administration method, 12-mL aliquots of phenytoin suspension were injected into the catheter by seven methods that varied with respect to catheter temperature, dilution of suspension, and irrigation of catheter. Each method was tested in triplicate, and samples were assayed by high-performance liquid chromatography. Varying the temperature of the catheter or suspension had little effect on the recovery of phenytoin. There was no appreciable loss of phenytoin when the suspension was undiluted, regardless of whether the catheter was irrigated. The greatest losses were seen when the suspension was diluted before administration. Irrigation also caused a decrease in recovery, but to a lesser extent than dilution. Until the effects of administering multiple doses of phenytoin through PEG Pezzer catheters are investigated, phenytoin suspension should not be diluted before administration because of decreased recovery and increased administration time.

Catheterization↗

Barium sulfate suspension as a negative oral MRI contrast agent: in vitro and human optimization studies.

In vitro proton spectroscopy with line-width measurements and MR imaging were performed on various concentrations of commercially available single contrast (SC), double contrast, oral and rectal barium sulfate suspensions, as well as potassium sulfate, barium chloride, barium hydroxide, and 97% pure barium sulfate suspensions. Approximately 500 ml of 20%, 40%, 60%, and 70% w/w suspensions of SC oral barium sulfate suspensions were administered to four normal volunteers, respectively, and MR images were obtained at both 1.5 T and 0.15 T. Subsequently, 500 ml of 60% w/w suspensions of SC oral barium sulfate suspensions were administered to five normal volunteers and imaged at 1.5 T. All of the inert suspensions produced line-width broadening but the SC oral barium sulfate suspension at 50% and 70% stayed in suspension even after hours of standing undisturbed. As much as 80% of the small bowel and the entire colon were well visualized using the combination of 60% or 70% w/w SC barium sulfate suspensions with SE 550/22 and FISP pulse sequences. The effect was less at 0.15 T and also with the SE 2000/45/90 pulse sequences. We conclude that barium sulfate suspensions are useful as oral MRI contrast agents.

Administration, Oral↗

Comparison of cell-suspension and explant culture of rabbit limbal epithelial cells.

Currently, most investigators directly use limbal explants to culture corneal epithelial cells. However, it has not been identified that limbal stem cells do readily migrate from the limbal explants onto culture plate or amniotic membrane carrier. In this study a cell-suspension culture system for rabbit limbal stem cells was developed and compared with the direct explant method in the aspect of stem cells content in the culture system. Rabbit limbal epithelial cells were dissociated from rabbit eyes by dispase and single cell suspension was made for cell-suspension culture. DeltaNp63 expression of cultured rabbit limbal epithelial cells by cell-suspension technique and explant technique was detected. In cell-suspension culture, isolated cell-suspension was evaluated by flow cytometric analysis for vimentin expression and residual limbal tissue after dispase treatment was examined by scanning electron microscopy. In limbal epithelial cells suspension less than 5% cells were vimentin positive. Examination of residual limbal tissue confirmed that all the limbal epithelial cells had been removed. Histological examination revealed that with cell-suspension culture the cultured epithelial cells could differentiate better than with explant technique. In cells cultured with cell-suspension, there were much more cells expressing DeltaNp63 than in explant cultured cells. In cells cultured with explants, most of DeltaNp63 labelling cells mustered around the explants, and peripheral cells on the slides were DeltaNp63 negative. These results suggested that with pure limbal epithelial cells suspension including basal cells, which could directly enter into culture system, cell-suspension culture technique was significantly superior to explant culture technique in terms of stem cells content.

Animals↗

Suspension systems for prostheses.

The appropriate suspension system results in a safe and well functioning lower extremity prosthesis. Residual limb length, joint ligament stability, and limb volume determine suspension methods as does activity level, dexterity, success of previous suspension, and cosmetic requirements. The supracondylar suspension cuff, prosthetic sleeves, and gel liners with locking mechanisms generally are indicated for the average to long transtibial amputation level. Short limbs are better fitted with supracondylar and suprapatellar suspension. Waist belts generally are indicated for patients with new amputations or those with vascular compromise. Suction suspension is the most desirable form of transfemoral suspension and is recommended for most standard to long residual limbs. Roll on silicone liners with or without locking pins and the hyperbaric sock offer the patient systems that are easier to don yet still provide unencumbered suspension. The total elastic suspension belt offers excellent auxiliary suspension and can be applied to the prosthesis by the patient. Multiple factors and patient preference should be considered when prescribing suspension systems for lower extremity prostheses.

Artificial Limbs↗

Improved continence after radical retropubic prostatectomy using two pubo-urethral suspension stitches.

OBJECTIVES: To determine if placement of urethral suspension stitches during radical retropubic prostatectomy improves postoperative urinary continence. METHODS: Between January 1997 and January 1998 we performed radical retropubic prostatectomy on 50 men. The first 25 consecutive men had their surgery without urethral suspension stitches while the next 25 received placement of two anastomotic urethral suspension stitches anchored to the lower portion of the pubic bone. Patients were interviewed six months postoperatively and each underwent valsalva leak-point pressure measurement. Patients were categorized as either completely continent (requiring no pads and having no measurable valsalva leak point), socially continent (zero or one pad per day), or incontinent (two or more pads per day). RESULTS: In the urethral suspension group, 8/25 (32%) patients were completely continent and did not have a measurable valsalva leak-point pressure while 3/25 (12%) without urethral suspension were completely continent. Of the remaining patients in the urethral suspension group, 13/17 (76%) patients were socially continent while 4/17 (24%) were incontinent. The mean valsalva leak-point pressure in the 17 patients with suspension stitches was 89.6 +/- 21.6 cm H2O. In the patients without urethral suspension, there were 22 patients who had some degree of incontinence. Among non-stitch patients, 13/22 (59%) were socially continent while 9/22 (41%) were incontinent. The average valsalva leak-point pressure in these patients was 74.0 +/- 16.7 cm H2O, which was significantly lower than those with the suspension (p = 0.015). CONCLUSIONS: Placement of anastomotic urethral suspension stitches during radical retropubic prostatectomy may increase the likelihood of complete postoperative urinary continence. The urethral suspension stitches also increase valsalva leak-point pressure, which may improve the percentage of patients with socially acceptable incontinence.

Humans↗

Effect of tail suspension on haemodynamics in intact and sympathectomized rats.

The effect of a 2-week tail suspension on mean arterial pressure (MAP) and pulse interval (PI) was studied in conscious chronically instrumented intact and sympathectomized rats. Sympathectomy was induced by 6-hydroxydopamine (100 mg x kg(-1), i.v.), injected 1 day before, and on days 5 and 10 of suspension. During suspension the intact rats had the same levels of MAP and PI as the intact controls. After release from suspension their MAP did not change: PI decreased (by 9%), but only for 1 h. Sympathectomy augmented the haemodynamic changes after release from suspension: tachycardia (10%) and hypotension (19%) were observed during the entire recording period (2 h). Therefore, in rats, post-suspension hypotension becomes apparent only after elimination of sympathetic influences. In spite of unaltered systemic parameters, intact post-suspension rats showed diminished responses to intravenous administration of tyramine (100 microg x kg(-1)) and phenylephrine (1-2 microg x kg(-1)). In addition, they showed augmented haemodynamic changes associated with natural behaviour. The increase of MAP and the decrease of PI on transition from rest to movement were more pronounced in the intact post-suspension rats than in the control rats (MAP 8.3% vs 4.5%, PI 15% vs 9%). In control rats the spectrum power density of low-frequency (0.0195-0.25 Hz) MAP fluctuations depended only weakly on behavioural activity, whereas in post-suspension intact rats it was profoundly augmented during movements (by 170%). Since the rapid adjustment of haemodynamics to behavioural activity is controlled by the sympathetic nervous system, the unbalanced condition of the cardiovascular system after suspension may reflect an altered sympathetic nerve control of the circulation.

Animals↗

NOS II inhibition attenuates post-suspension hypotension in Sprague-Dawley rats.

The reduction in mean arterial pressure observed in astronauts may be related to the impairment of autonomic function and/or excessive production of endothelium-derived relaxing factors. Here, we examined the role of a nitric oxide synthase II (NOS II) inhibitor AMT (2-amino-dihydro-6-methyl-4H-1,3-thiazine) against the post-suspension reduction in mean arterial pressure (MAP) in conscious male Sprague-Dawley rats. Direct MAP and heart rate were determined prior to tail-suspension, daily during the 7-day suspension and every 2 hrs post-suspension. Prior to release from suspension and at 2 and 4 hrs post-suspension, AMT (0.1 mg/kg), or saline, were administered intravenously. During the 7-day suspension, MAP was not altered, nor were there significant changes in heart rate. The reduction in MAP post-suspension in saline-treated rats was associated with significant increases in plasma nitric oxide and prostacyclin. 2-Amino-dihydro-6-methyl4H-1,3-thiazine reduced plasma nitric oxide levels, but not those of prostacyclin, attenuated the observed post-suspension reduction in MAP and modified the baroreflex sensitivity for heart rate. Thus, the post suspension reduction in mean arterial pressure is due, in part, to overproduction of nitric oxide, via the NOS II pathway, and alteration in baroreflex activity.

Animals↗

Taste comparison of corticosteroid suspensions.

OBJECTIVE: Although numerous taste studies have compared the palatability of antibiotic suspensions, few have compared the palatability of corticosteroid suspensions. Therefore, we compared the taste of 8 commonly prescribed liquid corticosteroid suspensions with the intent to help guide prescribing practices and improve patient compliance. METHODS: We conducted a randomized, double-blind study using 31 adult volunteers ages 24 to 57. All volunteers were asked to sample 8 different pediatric corticosteroid suspensions and to rate the palatability of their taste and aftertaste. The mean scores for each sample were then compared. RESULTS: The 8 suspensions fell into 2 groups based on their taste scores: one group with relatively high scores or more acceptable tastes (Orapred, Pediapred, and a dexamethasone suspension) and a second group with relatively low scores or less acceptable tastes (a prednisone suspension and 4 cherry-flavored prednisolone suspensions). CONCLUSIONS: The results demonstrate a significant difference in palatability between corticosteroid suspensions. Not only will this new information help clinicians choose between otherwise equivalent corticosteroid suspensions but, given the importance children place on taste, may improve compliance as well.

Administration, Oral↗

Palatability and relative bioavailability of an extemporaneous carbamazepine oral suspension.

The palatability of five flavored and unflavored extemporaneous carbamazepine 20-mg/mL oral suspensions was tested, and the bioavailability of the unflavored suspension relative to that of the tablet used in its manufacture was determined in a randomized, crossover study of 12 healthy volunteers. Carbamazepine 400 mg was administered with a glass of water as either 20 mL of unflavored oral suspension (20 mg/mL) or two 200-mg tablets. Subjects were randomly assigned to receive first either the tablets or the suspension in crossover fashion on two days separated by at least two weeks. Blood samples were taken just before and at various times up to 72 hours after the carbamazepine dose. Serum samples were assayed for carbamazepine content by high-performance liquid chromatography. Of five flavored and unflavored carbamazepine suspensions tested in eight volunteers, the cherry-mint formulation was the least palatable. There was no trend in preference among the remaining suspensions (banana, tutti-frutti, grape, and unflavored). Mean values of maximum serum concentration and absorption rate constant were significantly greater for the unflavored suspension (5.7 mg/L [24 mumol/L] and 0.832 hr-1, respectively) than for the tablet (4.9 mg/L [20.8 mumol/L] and 0.266 hr-1, respectively). The mean time to maximum concentration was significantly shorter after suspension administration (3.87 hours) than after tablet administration (11.8 hours). There was no significant difference in the extent of absorption of the tablet and suspension formulation as reflected by the corrected values of the area under the serum concentration-versus-time curves. The mean (+/- S.D.) bioavailability of the suspension relative to the tablet was 94.46% +/- 20.42 (range 76.35-132.72%).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Rheo-optical Behaviors and Stability of a Silica Particle Suspension Coated with Silane Coupling Agents.

The rheo-optical behaviors and suspension stability of silica particles coated with silane coupling agents were investigated experimentally. Mono-dispersed silica particles were synthesized by the sol-gel method and the particles were coated with silane coupling agents such as vinyltriethoxy silane (VTES) and gamma-methacryloxypropyl triethoxy silane (MPTES). Although all the suspensions of identical particle volume fraction exhibited similar rheological behaviors at high shear rates, only the stabilized suspensions coated with either VTES or MPTES displayed smooth shear thinning rather than abrupt change in the shear viscosity, as is typical of suspensions with no surface treatment. The present study showed that the MPTES coating was very effective in enhancing the phase stability compared to the VTES coating. The flow-induced dichroism for the MPTES-coated suspensions did not experience sign change, while those of the non-stabilized suspensions changed sign as the shear rate was increased. The VTES-coated suspensions underwent a transition from a stable to an unstable state as the particle volume fraction increased. Specifically, the rheological behaviors of the VTES-coated suspensions of particle volume fraction 0.35 were similar to those of the MPTES-coated suspensions. When the volume fraction exceeded 0.45, however, the effect of VTES coating diminished. Finally, the stress-optical rule proposed by Bender and Wagner was adopted to model the stabilized suspensions considered here. The present results indicated that the stress-optical coefficient could be predicted successfully by the proposed stress-optical rule if the contribution from the hydrodynamic interaction is considered separately from the thermodynamic contribution. Copyright 1998 Academic Press.

Journal Article↗

Dispersion of Silica Fines in Water-Ethanol Suspensions.

The dispersion of silica fines in water-ethanol suspensions has been studied through the measurement of settling efficiency, wetting rate, zeta potential, and viscosity. The measurements were performed on two silica samples with mean volumetric diameters of 5.02 and 0.272 &mgr;m at different fractions of ethanol in water-ethanol suspensions. The results have demonstrated that the dispersion stability of the silica suspensions increased as the fraction of ethanol increased and reached to maximum at the fraction of 50%, followed by a decline. The stability was stronger in a pure ethanol suspension than in a pure water suspension. It was observed that the stability closely correlated with the lyophilicity of the particles, but was not predominated by the surface charge of the particles as predicted by the DLVO theory. Viscosity measurements have been used to estimate the solvation film thickness on silica particles immersed in water-ethanol suspensions, on the basis of Einstein's theory of the viscosity of dispersions. It was found that the solvation film thickness on silica fines in a water-ethanol (1 : 1) suspension is about double that in a pure water suspension and about 1.4-fold that in a pure ethanol suspension, respectively, which well explains the dispersion behaviors of the silica fines in the water-ethanol suspensions because a thicker solvation film will cause a stronger disjoining pressure to prevent the proximity of the particles. Copyright 2001 Academic Press.

Journal Article↗

Flow cytometric analysis of protein content in Taxus protoplasts and single cells as compared to aggregated suspension cultures.

Plant suspension cultures are highly aggregated, preventing the direct application of flow cytometry for the study of population dynamics. The utility of single cells to accurately represent aggregated suspension cultures was tested through the analysis of total protein content. Specifically, protein content of two Taxus cuspidata suspension culture lines was studied using the Bradford assay for aggregated suspension cultures, and flow cytometry with fluorescein isothiocyanate staining for protoplasts and single cells. Taxus protein levels were measured at 75-160 mg per gram dry weight via the Bradford assay. Aggregated suspension cultures, protoplasts, and single cells predicted the same trend of protein content over the culture period (21 days). Normalized protein content of isolated single cells was statistically equivalent to aggregated suspensions for both cell lines. However, normalized protein content of isolated protoplasts showed significant differences from aggregated suspensions for one of the two cell lines. Elicitation with methyl jasmonate (MJ) is commonly utilized to increase paclitaxel accumulation in suspension cultures, and therefore the effect of MJ elicitation on protein content in aggregated suspensions, isolated single cells and protoplasts was assessed. Aggregated suspension cultures, protoplasts, and single cells did not show any change in total protein content following elicitation with MJ at 200 microM on day 7. This study illustrates the usefulness of flow cytometry for obtaining culture population information and the value of using intact single cells for the study of plant metabolism.

Cell Aggregation↗

Electromyography of rat soleus, medial gastrocnemius, and tibialis anterior during hind limb suspension.

Hind limb suspension is a model frequently utilized to study muscle plasticity. One reason for its frequent use is that it is thought to mimic in many respects the conditions imposed on some muscles during spaceflight. Changes in muscle properties that follow hind limb suspension generally have been attributed to reductions in the recruitment of these muscles. To determine the validity of this assumption, the electromyographic (EMG) activity of three hind limb muscles, the soleus, a slow extensor, the medial gastrocnemius, a fast extensor, and the tibialis anterior, a fast flexor, was studied. The EMG was recorded in each rat for 25 min of each hour for 24 consecutive hours, 7 and 3 days prior, on the day of, and 3, 7, 14, 21, and 28 days after hind limb suspension. Control rats were treated similarly and their EMG recorded on corresponding days. Compared with presuspension, soleus activity was reduced significantly to 91% on the first day of suspension, but had recovered to 81% of its normal activity by the seventh day. Similarly, there was a significant reduction to 54% in activity of the medial gastrocnemius on the day of hind limb suspension which recovered to 98% of its presuspension values by day 7. In contrast, the tibialis anterior showed a significant increase in activity relative to presuspension values within 3 days of the initiation of suspension. These data indicate that hind limb suspension produced only a relatively short-term reduction in the activity of both the soleus and medial gastrocnemius and results in an increased activity in the tibialis anterior. Collaborative studies showed that significant alterations in muscle mass and metabolic and mechanical properties occurred and persisted in spite of the recovery of activation in the soleus and medial gastrocnemius. In addition, no alterations in mass and mechanical properties were evident in the tibialis anterior during a 4-week suspension even though the EMG increased after hind limb suspension. Together, these data indicate that the adaptations in muscle properties following hind limb suspension are not closely related to changes in the total amount of muscle EMG activity per day.

Adaptation, Physiological↗

Evaluation of ophthalmic suspensions using surface tension.

Uniformity and precision of single dose are required for ophthalmic suspensions including water-insoluble ingredients. Solid sediments formed after standing still must be immediately re-dispersible and distributed homogeneously before use. However, selection of an appropriate water-soluble polymer as suspending agent is a challenging problem. In this report, the relationship between the surface tension and the re-dispersibility of suspensions was investigated. The surface tension of 0.1 w/v% fluorometholone suspensions began to decline from 74 mN/m at 0.0001 w/v% of hydroxypropylmethylcellulose (HPMC) and became almost constant at 52 mN/m at 0.01 w/v% of HPMC. Re-dispersion time was less than 4 s when HPMC was present at concentrations between 0.0001 w/v% and 0.01 w/v%. At these concentrations, aggregation of suspended particles was not observed. When indomethacin suspensions at 1.0 w/v% concentration were used, the surface tension began to decline from 73 mN/m at 0.0005 w/v% HPMC and became constant at 50 mN/m at 0.005 w/v% HPMC. The suspension also showed good re-dispersibility, and a uniform suspension was obtained between 0.0005 w/v% and 0.005 w/v% of HPMC. The time required for re-dispersion was less than 17 s. The change of surface tension showed a good correlation with the concentration of HPMC in ophthalmic suspensions having good re-dispersibility. Measurement of the surface tension of suspensions provided the optimal concentration of the water-soluble polymers for the suspensions of well re-dispersible characteristics. Evaluation of ophthalmic suspension using surface tension is a good strategy for formulation of suspending pharmaceutical products in the ophthalmic area.

Dose-Response Relationship, Drug↗