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Pharmaceutical suspensions: relation between zeta potential, sedimentation volume and suspension stability.

The effect of added surface-active agents of various ionic types on the sedimentation volume of drug suspensions of betamethasone, griseofulvin, nalidixic acid and thiabendazole has been investigated, and the results correlated with previously measured zeta potentials. Study of the zeta potential/sedimentation volumes versus concentration plots showed that apparently only coagulated, deflocculated or sterically stabilized systems were formed. In most cases the sterically stabilized systems were produced from mixtures of ionic/non-ionic surfactants. These are examples of controlled coagulation, although non-ionic surfactant alone conferred stability against caking. Secondary minimum flocculation was not apparent but this may have been due to the method of examination of suspensions. The work confirmed that the DLVO theory of colloid stability and its modification to include a steric term can be applied to coarse suspension systems.

Centrifugation↗

Omeprazole/antacid-powder suspension--Santarus: Acitrel, Rapinex Powder for oral suspension, SAN 05.

Santarus Inc., is developing an immediate-release formulation of omeprazole in combination with an antacid (sodium bicarbonate) as a powder for suspension, known as Acitrel [SAN 05], and also as Rapinex powder for oral suspension. Acitrel is based on technology licensed from the University of Missouri. Santarus have also licensed technology from Tulane and North Carolina Universities relating to potential treatments for GI diseases. Santarus have licensed exclusive, worldwide rights to patent applications covering specific combination-formulations of proton pump inhibitors and antacids for treating various upper GI diseases and disorders. Santarus plans to license development, distribution and marketing rights of Rapinex Powder for oral suspension 20mg outside the US, to one or more well established pharmaceutical companies. The US FDA has requested that Santarus pursue a name other than Rapinex for the product. Santarus is currently discussing potential alternative names for the product with the FDA. Santarus announced positive results, in August 2003, from a phase III trial comparing oral Acitrel (Rapinex 40mg) to intravenous cimetidine in preventing upper GI bleeding in 359 critically ill adult patients. Santarus has also completed an open-label clinical trial in 243 patients, including 97 patients with gastric ulcers, evaluating the safety of Rapinex 40mg for an 8-week period. In connection with the NDA for Rapinex 40mg, Santarus provided notice to the NDA holder for Prilosec delayed-release capsules and related patent owners that Rapinex 40mg does not infringe currently listed patents for Prilosec or that those patents are invalid.

Administration, Oral↗

Laparoscopic uterosacral ligament uterine suspension compared with vaginal hysterectomy with vaginal vault suspension for uterovaginal prolapse.

This study compares the outcomes of laparoscopic uterosacral ligament uterine suspension (LUSUS) to those of vaginal vault suspension with total vaginal hysterectomy (TVH) for the treatment of symptomatic uterovaginal prolapse. We compared the outcomes of 25 LUSUS to those of 25 TVH with vaginal vault suspension among age-matched controls. No significant complications occurred in either group. EBL and hospitalization duration were significantly less in LUSUS patients (72 cc vs. 227 cc, P < .0001 and 1.05 vs. 1.65 days, P = .002). Vault support, as measured by postoperative pelvic organ prolapse quantitation system point D in the LUSUS group and point C in the TVH group, was better for the LUSUS group (D = -9 vs. C = -7.6, P = .002). No LUSUS group patient underwent reoperation for recurrent apical prolapse as compared to three TVH patients. LUSUS is an effective treatment for appropriately selected women with uterovaginal prolapse who desire uterine preservation.

Adult↗

A comparative study of the efficacy and safety of fluconazole oral suspension and amphotericin B oral suspension in cancer patients with mucositis.

This randomized study compared the efficacy and safety of fluconazole suspension with that of amphotericin B suspension in patients with head and neck cancer who were suffering from candidiasis during cancer treatment with radiotherapy and/or chemotherapy. A total of 123 evaluable patients received 50 mg fluconazole once daily and 120 evaluable patients received 0.5 g amphotericin B thrice daily for 7-14 days depending on clinical response. A positive culture result was obtained in 121 of 264 (46%) patients; Candida albicans was most common. At the end of treatment, fluconazole and amphotericin B were equivalent (CI(90) of -10.7 to +14.9) in terms of clinical cure and improvement, but the rate of mycologic cure was higher for fluconazole (48%) than amphotericin B (35%). The incidence of adverse events was 39% for fluconazole and 44% for amphotericin B. Fluconazole suspension appeared effective and safe.

Administration, Oral↗

Pharmacokinetics of human insulin zinc suspension (recombinant DNA) in normal man: a comparison with porcine insulin zinc suspension.

A single dose crossover study in 10 fasting, non-diabetic men compared the 24-hour profiles of blood glucose, plasma insulin, and C-peptide following a single subcutaneous injection of either human insulin zinc suspension crystalline (recombinant DNA), or highly purified porcine insulin zinc suspension (mixed), in a standard dose of 0.2 U/kg. Both insulins produced moderate hypoglycaemia within 3 hours which persisted for 24 hours after administration. The rate of fall of blood glucose was similar from 0-3 hours but was significantly lower after the porcine insulin at 4 and 7 hours (p less than 0.05). Mean plasma insulin values were higher after porcine insulin between 2 and 6 hours (p less than 0.05) and a biphasic pattern was observed following injection of both insulins. Plasma C-peptide declined after each insulin was administered, and was significantly lower between 2 and 7 hours after porcine insulin. The duration of the hypoglycaemic action of human crystalline insulin (recombinant DNA), assessed by blood glucose measurements and C-peptide suppression, was equivalent to porcine insulin zinc suspension (mixed) (Monotard MC, Novo) over 24 hours.

Adult↗

Comparison of the Stamey bladder neck suspension procedure with a modified endoscopic suspension for the treatment of stress urinary incontinence.

Endoscopic vesicourethral suspension is an acceptable procedure for the treatment of stress urinary incontinence and is associated with a high success rate and little morbidity. Classical endoscopic vesical neck suspension was performed in 93 patients with cure of incontinence in 89 (95.7%). Cost-effectiveness and simplification were introduced to Stamey's technique. Modifications introduced to the Stamey technique were found to be simpler and to provide cost savings with fewer complications. Eighty-six women were operated on by this method, with 84.9% of success. A total of 133 (74.3%) of the patients had previous surgical procedures to correct incontinence, demonstrating the indication of the endoscopic vesicourethral suspension in case of failures with other techniques.

Adult↗

Quantification of prosthetic outcomes: elastomeric gel liner with locking pin suspension versus polyethylene foam liner with neoprene sleeve suspension.

For this randomized crossover trial, we compared two common transtibial socket suspension systems: the Alpha liner with distal locking pin and the Pe-Lite liner with neoprene suspension sleeve. Our original hypotheses asserted that increased ambulatory activity, wear time, comfort, and satisfaction would be found with the elastomeric suspension system. Thirteen subjects completed the study. Following 2.5-month accommodation to each condition, ambulatory activity was recorded (steps/minute for 2 weeks), and subjects completed three questionnaires specific to prosthesis use and pain: the Prosthesis Evaluation Questionnaire (PEQ), a Brief Pain Inventory (BPI) excerpt, and the Socket Comfort Score (SCS). Upon completion, subjects selected their favored system for continued use. Ten subjects preferred the Pe-Lite and three the Alpha. Subjects spent 82% more time wearing the Pe-Lite and took 83% more steps per day. Ambulatory intensity distribution did not differ between systems. No statistically significant differences were found in questionnaire results. Subject feedback for each system was both positive and negative.

Adult↗

Intracerebral grafting of neuronal cell suspensions. III. Activity of intrastriatal nigral suspension implants as assessed by measurements of dopamine synthesis and metabolism.

The activity of intrastriatal grafts of nigral cell suspensions has been monitored biochemically, using radioenzymatic assays of dopamine, its major acidic metabolite, DOPAC, and DOPA accumulation after DOPA-decarboxylase inhibition. Implants of 4-9 microliter of nigral cell suspension restored striatal DA levels by an average of 13-18%, with the highest individual values reaching about 50% of control. DOPAC was restored from about 5% in the lesioned controls to about 20% of normal in the grafted animals. The DOPAC: DA ratios and the DOPA accumulation measures indicated that the grafted DA neurons were spontaneously active and that the transmitter turnover rate was on the average some 50-100% higher than the intact intrinsic nigrostriatal DA neurones. These results thus provide evidence that the intrastriatal nigral suspension grafts are capable of restoring dopaminergic neurotransmission in the previously denervated striatum.

Animals↗

Intracerebral grafting of neuronal cell suspensions. VI. Survival and growth of intrahippocampal implants of septal cell suspensions.

The survival and growth of intrahippocampal septal suspension grafts were investigated by acetylcholine esterase (AChE) histochemistry in animals with lesions of the intrinsic septohippocampal cholinergic pathways. AChE was demonstrable in the grafts after the first postoperative week, and AChE-positive fibres were seen to extend into the host hippocampus by 3 weeks. Rapid fibre outgrowth occurred between 3 weeks and 3 months after grafting, and continued at a slower rate thereafter. By 6 months a fairly complete reinnervation of the initially denervated hippocampus was achieved in most specimens, and this persisted at 14 months, the longest postoperative time analysed. A comparison between the development of the AChE-positive neurones in the suspension grafts with that seen during ontogeny in situ suggested that the grafted neurones lagged behind normal development by at least 1 week. Similar to our previous observations on septal grafts implanted as solid tissue pieces, the pattern of the newly-formed AChE-positive innervation in the host hippocampal formation, established from the septal suspension grafts, was remarkably similar to that of the normal AChE-positive septal innervation. This pattern became established as soon as the graft-derived fibres first grew in, suggesting that the ingrowing axons extended and ramified preferentially into those hippocampal subfields which normally receive an AChE-positive innervation from the septal-diagonal band area.

Acetylcholinesterase↗

Intracerebral grafting of neuronal cell suspensions. II. Survival and growth of nigral cell suspensions implanted in different brain sites.

Dissociated dopamine-rich cell suspensions were prepared from the ventral mesencephalon of rat embryos and injected in one or several sites in striatal and non-striatal regions in the dopaminergically denervated brain of adult rats. While the grafts survived well in all sites, the dopamine fibre outgrowth was markedly different depending on whether the grafts occurred in an area normally innervated by the mesencephalic dopamine neurones (i.e. neostriatum or nc. accumbens) or in areas not normally innervated by these neurones (i.e. parietal cortex, lateral hypothalamus or substantia nigra). Moreover, in grafts placed at different sites along the trajectory of the nigrostriatal pathway the outgrowing fibres remained confined to the graft, and there was little evidence that the implanted neurones could elongate their axons along the pathway of the nigrostriatal tract to reach the striatum from a distance. Thus, the intracerebral suspension grafts provided efficient reinnervation of a denervated target only when placed in the immediate vicinity of the target area. The results of multiple graft placements indicate that a relatively complete restoration of a lost innervation should be possible to achieve in large areas of the brain, such as the striatal complex, with the suspension grafting technique.

Animals↗

Double-blind clinical, endoscopic and histological comparison of hydrotalcite/dimethicone suspension and magnesium hydroxide/aluminum hydroxide suspension in the treatment of symptomatic gastritis.

A double-blind, randomized trial was undertaken to compare the clinical, endoscopic and histological response to 6-weeks' treatment with hydrotalcite/dimethicone suspension or magnesium hydroxide/aluminum hydroxide suspension in 36 patients with symptomatic gastritis. Significantly more patients (P less than 0.05) showed symptomatic improvement in the antacid-treated group than in the hydrotalcite/dimethicone-treated group and more had a reduction in histological inflammatory scores (P less than 0.01), although there was little correlation between histology and symptoms. There was no evidence from this study that the bile acid binding and anti-foaming properties of hydrotalcite/dimethicone suspension were of any benefit in the treatment of patients with symptomatic gastritis.

Adult↗

[Clinical and experimental study of treating aplastic anemia with fetal liver cell suspension and fetal liver cell-free suspension].

Fresh fetal liver obtained from 3- to 6-month fetus was prepared. Fetal liver cell suspension (FLC) or fetal liver cell-free suspension (FLCF) were then transfused into two groups of patient of aplastic anemia. 15 of 21 patients of aplastic anemia treated with FLC showed reconstitution of haemopoietic function or improvement of peripheral blood pictures, while 27 of 30 patients treated with FLCF showed reconstitution or improvement. It is verified that there is a stimulating factor for CFU-CM, BFU-E, and CFU-E and also a immunologic stimulant for improving the nonspecific immunologic function of the organism as shown by clinical analysis and experimental study. It is obvious that the therapeutic effect of FLCF is much better than that of the FLC.

Adolescent↗

Factors affecting yield and survival of cells when suspensions are subjected to centrifugation. Influence of centrifugal acceleration, time of centrifugation, and length of the suspension column in quasi-homogeneous centrifugal fields.

The goals of the centrifugation of cell suspensions are to obtain the maximum yield of cells with minimum adverse effects of centrifugation. In the case of mechanically sensitive cells such as mouse sperm, the two goals are somewhat contradictory in that g-forces sufficient to achieve high yields are damaging, and g-forces that yield high viability produce low yields. This paper mathematically analyzes the factors contributing to each goal. The total yield of pelleted cells is determined by the sedimentation rate governed by Stokes' Law, and depends on the relative centrifugal force, centrifugation time, size and shape of the cells, density of the cells and medium, viscosity of the medium, and the length of the column of suspension. Because in the situation analyzed the column is short relative to the rotor radius, the analysis considers the centrifugal field to be quasi-homogeneous. The assumption is that cells are not damaged during sedimentation, but that they become injured at an exponential rate once they are pelleted, a rate that will depend on the specific cell type. The behavior is modeled by the solution of coupled differential equations. The predictions of the analysis are in good agreement with experimental data on the centrifugation of mouse sperm.

Animals↗

Clarithromycin suspension vs penicillin V suspension in children with streptococcal pharyngitis.

Clarithromycin, an advanced-generation macrolide antibiotic, has demonstrated excellent in vitro activity against group A beta-hemolytic streptococcus (GABHS). Potent activity against Streptococcus pyogenes and a favorable pharmacokinetic profile have made it a reasonable alternative for treatment of patients with streptococcal pharyngitis. The safety and efficacy of clarithromycin and penicillin V were compared in a randomized, investigator-blind study. Children 6 months to 12 years of age received 5 days of clarithromycin suspension 7.5 mg/kg twice daily (n = 268) or 10 days of penicillin V suspension 13.3 mg/kg three times daily (n = 260). Patients were evaluated for signs and symptoms of pharyngitis, and throat swabs for culture were obtained prior to therapy, at the end of therapy, and at follow-up. Clarithromycin and penicillin V produced comparable rates of clinical success (cure + improvement) at the posttreatment (97% and 94%) and follow-up (81% and 82%) evaluations. The GABHS eradication rate, however, was significantly higher with clarithromycin (94% vs 78%, P < .001). Both drugs were well tolerated; gastrointestinal complaints were similar and mild. Resistance did not occur with the short course of clarithromycin or the standard regimen of penicillin V. Five days' treatment with clarithromycin was superior to 10 days of penicillin in eradicating S. pyogenes.

Analysis of Variance↗

Detection of sperm surface related antibodies by indirect immunofluorescence test on sperm suspensions. Indirect IFT on sperm suspensions.

An indirect immunofluorescence test (IIFT) using sperm suspensions was carried out on 20 sera with sperm agglutinins (SA) and on 25 negative controls. IIFT gave results highly correlated with the occurrence of sperm agglutinating activity. Moreover, a relation was found among class of Ig involved in IF reactivity, fluorescent stain pattern and type of sperm agglutinations. In all sera with "mixed" or "tail-tail" sperm agglutinating activity, IgG were involved in IF reactivity; the fluorescent stain constantly appeared in a granular pattern along the sperm tail and most often on the head surface too. In relation to high titres of "head-head" sperm agglutinating activity, IgM were involved in IF reactivity; here the fluorescent stain appeared to be localized on acrosomal surface. The results indicate that indirect IFT on sperm suspensions specifically detects sperm surface related antibodies.

Antigens, Surface↗

Comparative Study of the Efficacy and Tolerability of Secnidazole Suspension (single dose) and Tinidazole Suspension (two days dosage) in the Treatment of Amebiasis in Children.

Amebiasis caused by Entamoeba histolytica may be considered the most aggressive parasitic disease affecting human intestine, causing acute amoebic colitis and extra-intestinal diseases of high morbidity and mortality. 5-nitroimidazoles are the drugs of choice. In this multicenter, open and random clinical trial, the efficacy and tolerability of secnidazole suspension in a single oral dose of 1ml/kg was compared with 0.5ml/kg doses of tinidazole suspension given for 2 consecutive days to 303 Entamoeba histolytica-positive children aged 2 to 13. Patients with extra-intestinal complications were excluded from the study. Clinical and parasitological follow-up using the Faust and Kato-Katz method were carried out 7, 14, and 21 days after treatment. Clinical improvement/cure was observed in 93% of the patients in the secnidazole group and 91% in the tinidazole group. Parasitological success was reported for 77% and 63% of the secnidazole and tinidazole patients, respectively, showing a significant statistical difference between the two groups (p=0.007). Both drugs were well tolerated, and the adverse effects reported were mild, consisting mainly of digestive disturbances. This comparative study showed that a single oral dose of 1ml/kg of secnidazole produced a significantly higher parasitological cure rate than 2 doses of tinidazole. Secnidazole is a safe and effective drug for the treatment of uncomplicated intestinal amebiasis.

Journal Article↗

Intracerebral grafting of neuronal cell suspensions. V. Behavioural recovery in rats with bilateral 6-OHDA lesions following implantation of nigral cell suspensions.

Bilateral 6-hydroxydopamine-induced lesions of the ascending forebrain dopamine neurones induce a behavioural syndrome in rats which includes profound aphagia, adipsia, akinesia and bilateral sensorimotor neglect. Such animals will die unless maintained by intragastric feeding. Three experiments are reported in which we have attempted to ameliorate this syndrome with single or multiple placements of nigral cell suspensions into the forebrains of rats with bilateral dopamine depletions. Although the grafts were efficient in reversing the sensorimotor and akinetic impairments, and produced a significant increase in eating, the grafted rats remained hypophagic and adipsic. The results indicate that although many components of the bilateral dopamine denervation syndrome can be reversed by intrastriatal nigral suspension grafts, the severe eating and drinking deficits remain unameliorated.

Animals↗

Intracerebral grafting of neuronal cell suspensions. VII. Recovery of choline acetyltransferase activity and acetylcholine synthesis in the denervated hippocampus reinnervated by septal suspension implants.

The time-course and magnitude of fibre outgrowth from septal suspension grafts injected into the previously denervated hippocampal formation was monitored by measurements of choline acetyltransferase (ChAT), and the activity of the grafted neurons was assessed by measurements of [14C]acetylcholine (ACh) synthesis from [14C]glucose in vitro. Graft-derived ChAT activity was barely detectable 10 days after grafting, but increased sharply between 10 days and 1 month in the areas of the hippocampus located close to the septal implants. By 6 months ChAT activity was restored to near normal levels in all segments of the previously denervated hippocampus. The overall hippocampal [14C]ACh synthesis was also restored to normal levels in the grafted animals, and estimates of the ACh turnover rate suggested that the transmitter machinery of the newly established "septo-hippocampal" connections operated at a rate similar to that of the intrinsic septohippocampal pathway. The intrahippocampal septal suspension grafts, similar to the intrastriatal nigral grafts, thus seem to be capable of maintaining function at a relatively "physiological" level despite their abnormal positions.

Acetylcholine↗