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PubMed1976

Limitations of compounding diazepam suspensions from tablets.

The concentration of diazepam in two types of suspension vehicles, as prepared from 10-mg tablets was tested over a 14-day period. The suspensions (1 mg/ml) were stored at room temperature in amber glass bottles. In one suspension, consisting of eight triturated tablets, 4.0 ml ethanol, 24.0 ml propylene glycol, 20.0 ml Syrup, USP, and 32.0 ml chocolate syrup, 90% of the diazepam was dissolved. This suspension demonstrated consistently acceptable concentrations of diazepam. In the other suspension, consisting of triturated tablets and Syrup, USP, only 25% of the diazepam was dissolved, and less consistent, subpotent concentrations of diazepam were found. The variation of diazepam concentrations between the suspensions was unrelated to the chemical stability of the drug.

Diazepam↗
PubMed2003

Effects of gravitational loading on rat soleus muscle fibers following hindlimb suspension.

Effects of 16 days of hindlimb suspension and 16 days of ambulation recovery at 1-G or 2-G environment on the characteristics of soleus muscle fibers were studied in male Wistar Hannover rats. The mean cross-sectional area and myonuclear number in isolated single fibers at the termination of suspension were approximately 30% and 25% of the controls, respectively. Satellite cells were distributed evenly throughout the fiber length in the control. However, the number of satellite cells distributed at the middle of the fiber was less in the unloaded rats immediately after the termination of suspension. Both the numbers of quiescent and mitotic active satellite cell per fiber were approximately 57% less immediately after the termination of suspension than controls. The number of satellite cells at the end of fibers was increased first during the early phase of reloading. Subsequently, the number at the middle was gradually increased. The myonuclear number per fiber was also less (approximately 25%) in the unloaded than the age-matched control at the termination of suspension, but was increased following the recovery. Although the mean in vivo sarcomere length of the soleus muscle was shortened in response to plantarflexion of ankle joint, the length at the certain ankle joint angle was increased after 16 days of suspension due to sarcomere remodeling. The length at the proximal and distal, rather than the middle, portion of the fiber was stretched in both reloaded and control rats in response to dorsiflexion of the ankle joint. But it was noted that the magnitude of stretch was greater in the unloaded rats. It is suggested that the fiber end is more stimulated rapidly than the middle portion by the load applied to the muscle during the ambulation recovery.

Animals↗
PubMed2003

Pulsatile and sustained peptides release from Zn(II) suspensions.

The dynamics of peptide release from suspensions in the form of solid, sparingly soluble Zn(II)-Peptide complexes in molar ratio 50:1 was observed in vitro conditions. Thyroliberine and dalareline release from suspensions is statistically significant in comparison with gonadrenaline release. Pulsatile character of peptide release in 6 significant peaks of released dalareline, 5--of gonadoreline release and 4--thyroliberine were observed. Thyroliberine was released fastest from the obtained suspensions--63 h +/- 3.1, and dalareline was released slowest--26.5 h +/- 2.3. The release time for gonadoreline from suspensions was 12.0 h +/- 1.0. Molecular weight of the peptide and properties of the Zn(II)-Peptide complexes have major influence upon the character and time of peptide release from suspensions. The greater is the molecular weight and durability of Zn(II)-Peptide complex, the bigger is the number of peaks of the peptide released from suspensions. The release time of the peptides is longer when the molecular weight of the released peptide is bigger.

Delayed-Action Preparations↗
PubMed2004

Improvement of physical stability and dissolution rate of celecoxib suspensions by complexation with beta-cyclodextrins.

Solid dispersions of celecoxib with beta-cyclodextrins were prepared by physical mixing, slugging and kneading methods at 1:1 and 1:2 molar ratios and characterized by differential scanning calorimetry. Celecoxib suspensions were formulated employing its solid dispersions with sodium carboxymethylcellulose as the suspending agent. Stability studies were conducted by subjecting all the suspensions to freeze-thaw cycling. The suspensions were evaluated for particle size, sedimentation volume, viscosity, redispersibility and dissolution rate initially and after stability testing. Celecoxib suspensions formulated employing its solid dispersions exhibited good physical stability and gave higher dissolution rates than those formulated with celecoxib alone. The suspension prepared from solid dispersions (1:2) by the kneading method gave the highest improvement in dissolution rate and efficiency. Celecoxib in the inclusion complex with beta-cyclodextrin produced suspensions of better physical stability and dissolution rate.

Calorimetry, Differential Scanning↗
PubMed1991

Stability of acetazolamide in suspension compounded from tablets.

The stability of acetazolamide in an extemporaneous suspension compounded from tablets was studied. Acetazolamide 25-mg/mL suspension was prepared by levigating the comminuted 250-mg tablets with 70% sorbitol solution. The mixture was incorporated into a suspension vehicle containing magnesium aluminum silicate and carboxymethylcellulose sodium. Appropriate sweeteners, flavoring agents, preservatives, humectants, and pH adjusters were then added. The suspension was stored in amber glass bottles at 5, 22, 30, 40, and 50 degrees C. Samples were analyzed for the concentration of acetazolamide by stability-indicating high-performance liquid chromatography on days 3, 7, 11, 18, 24, 32, 42, 54, and 79. For batches stored at 5, 22, and 30 degrees C, the initial acetazolamide concentration was maintained during the entire 79 days of the study. However, the concentrations in the batches stored at 40 and 50 degrees C were below 90% of the initial value after 79 and 32 days, respectively. The Arrhenius plot was used to predict a shelf life of the suspension at room temperature of 371 days. Acetazolamide oral suspension 25 mg/mL was stable for at least 79 days at 5, 22, and 30 degrees C. The formulation should be maintained at pH 4-5 and stored in amber glass bottles.

Acetazolamide↗
PubMed1990

Loss of carbamazepine suspension through nasogastric feeding tubes.

The apparent loss of carbamazepine suspension during administration through polyvinyl chloride nasogastric feeding tubes in vitro was studied. Twelve methods of administering carbamazepine suspension (100 mg/5 mL) were tested; the methods differed with respect to nasogastric tube size, presence and type of diluent, and type of flush solution. Undiluted or 50% diluted carbamazepine suspension 200 mg was drawn up in a syringe and forced through adult or pediatric nasogastric feeding tubes. The tubes were immediately flushed twice with 50 mL of sterile water, 0.9% sodium chloride solution, or 5% dextrose solution, by using the same syringe used to administer the suspension. Samples were collected and analyzed for carbamazepine concentration by high-performance liquid chromatography. Each administration method was tested six times, and the results were subjected to analysis of variance. Significant loss of carbamazepine was noted for four of the six methods in which undiluted suspension was administered. In these methods, adult and pediatric tubes were flushed with sterile water or 0.9% sodium chloride. No significant loss of drug occurred for any of the methods involving the use of diluent. Significant losses were associated with diluent and flush solution but not nasogastric tube size. Carbamazepine suspension should be mixed with an equal volume of diluent before being administered through nasogastric feeding tubes.

Carbamazepine↗
PubMed1990

Platelet membrane responses to surface and suspension activation.

Exposure of blood platelets to foreign surfaces or to potent agonists in suspension results in dramatic changes in physical appearance and conversion from a nonsticky state. The transformation to the sticky state is associated with exposure of the fibrinogen receptor, GPIIB-IIIa, which is hidden in resting, discoid platelets. Recent studies employing fibrinogen coupled to gold (Fgn-Au) as an electron-dense probe have suggested that GPIIb-IIIa receptors not only become exposed in surface-activated platelets, but undergo a reorganization not observed in suspension-activated cells. Discoid platelets do not bind Fgn-Au; however, the bodies and extended pseudopods of dendritic forms are covered with Fgn-Au particles. Conversion of dendritic platelets to spread forms is accompanied by movement of receptor-ligand complexes away from peripheral margins into a concentrated mass in cell centers over the inner filamentous zone of the cytoplasm. Movement of the Fgn-Au particles to cell centers during spreading was considered due to the transmembrane action of the newly assembled actin filaments. We have carried out similar experiments on surface- and suspension-activated platelets with Fgn-Au and latex particles. GPIIb-IIIa receptors move Fgn-Au particles on outer membranes of surface- and suspension-activated platelets to channels of the open canalicular system. Treatment with cytochalasin B prevents assembly of actin filaments in surface- and suspension-activated platelets, and dissociates residual actin from the cell membranes, circumferential microtubules and organelles with which they interact. However, cytochalasin B does not prevent removal of Fgn-Au to channels of the open canalicular system. Thus, reorganization of fibrinogen receptors on surface- and suspension-activated platelets is due to the particles, and not to the fibrinogen, although fibrinogen is required to link gold to the receptor. The surface membrane has its own detergent and cytochalasin B-resistant cytoskeleton for directed transport of ligand-receptor complexes, independent of the internal assembly and contraction of actin into an inner filamentous zone.

Blood Platelets↗
PubMed1989

Concentration uniformity of extemporaneously prepared ranitidine suspension.

The concentration uniformity of an extemporaneously prepared ranitidine suspension was studied. To prepare the ranitidine suspension, 36 150-mg tablets were pulverized and suspended in 180 mL of distilled water. This mixture was diluted with simple syrup to a total volume of 360 mL, resulting in a final ranitidine concentration of 150 mg/10 mL. Samples from each of three bottles that had been filled with 60 mL of the suspension were assayed for ranitidine content by high-performance liquid chromatography. The sedimentation of suspended ranitidine tablet particles was studied by visual observation of the setting process in 10-mL samples from the same batch. The overall mean concentrations (in milligrams per milliliter) of ranitidine were 14.53, 15.25, 13.92, 12.67, and 12.72 at 0, 3, 7, 14, and 21 days, respectively. Compared with baseline, the difference in the ranitidine concentration was not significant over days 0-7. The ranitidine concentration was significantly reduced during the following time intervals: days 0-14, days 0-21, and days 7-21. In the settling experiments, the mean time (+/- S.D.) for sediment to first appear on the test tube bottom was 14.67 +/- 5.35 seconds. Approximately 40-50% (mean level = 3.2 mm) of the total sedimentation level (mean level = 7.3 mm) was observed one minute after shaking. The uniformity of ranitidine suspensions compounded according to procedures described in this report possibly could be improved with sonication. The ranitidine suspension should be well shaken, the dosage should be measured immediately after shaking, and the suspension should be used within seven days of compounding.

Chemistry, Pharmaceutical↗
PubMed1986

Formulation and stability of diazepam suspension compounded from tablets.

The stability of diazepam in an extemporaneous suspension compounded from tablets was studied. A diazepam 1 mg/mL suspension was prepared by levigating diazepam 10-mg tablets with ethanol and propylene glycol and incorporating them into a suspension vehicle containing magnesium aluminum silicate and carboxymethylcellulose sodium with flavoring and sweetening agents. Samples of the suspension were stored in amber glass bottles at 5, 22, and 40 degrees C. At various times during the 60-day study period, samples were inspected visually for signs of caking or color change and evaluated for ease of pouring and redispersion. Also at those times, the concentration of diazepam in each sample was determined by a stability-indicating, high-performance liquid chromatography procedure. The concentration of diazepam in each sample was at least 90% of the initial concentration throughout the 60-day storage period. All samples remained homogeneous and showed no signs of caking or settling. A diazepam suspension compounded from tablets was found to be pharmaceutically acceptable and easily pourable and redispersible. The suspension is stable for at least 60 days at room or refrigerated temperature.

Chromatography, High Pressure Liquid↗
PubMed1979

[Bioavailability of ampicillin suspensions].

The rate of ampicillin transfer into solution from suspensions of 2 types, i.e. suspensions of anhydrous ampicillin and suspensions of ampicillin trihydrate was studied. Conditions for estimation of the rate of ampicillin dissolution from the suspensions were developed. The pharmacokinetics of the pharmaceutical forms was studied on dogs. Definite advantages of the anhydrous ampicillin suspension were shown as compared to the ampicillin trihydrate suspension.

Ampicillin↗
PubMed1997

[Formulation and stability of suspensions for preclinical study].

In preclinical studies, poorly soluble drugs are usually administered orally to experimental animals as suspensions. The present study was aimed at providing data allowing predictive estimations of the stability of such suspensions. To this purpose aqueous suspensions of three drugs (griseofulvin, ibuprofen and indomethacin) were prepared at different concentrations using four different suspending agents: sodium carboxymethylcellulose (CMC), microcrystalline cellulose/carboxymethylcellulose (MC/CMC), hydroxypropylmethylcellulose (HPMC) and jota carragenaan (CJ). The physical and physico-chemical characteristics of the drugs, the rheological properties of the suspending media and of the corresponding drug suspensions, and the physical and chemical stability of the suspensions was then evaluated. The type of suspending agent, rather than the physical characteristics of the drug, appeared to exert the main influence on the physical stability of suspensions. The most stable formulations were produced by suspending agents with low-temperature gelation characteristics (CJ) or with thixotropic flux (MC/CMC).

Chemical Phenomena↗
PubMed2006

Retroviral vector production using suspension-adapted 293GPG cells in a 3L acoustic filter-based perfusion bioreactor.

Recombinant retroviruses are now an established tool for gene delivery. Presently they are mainly produced using adherent cells. However, due to the restrictive nature of adherent cell culture, this mode of production is hampered by low cell-specific productivity and small production units. The large-scale production of retroviral vectors could benefit from the adaptation of retrovirus packaging cell lines to suspension culture. Here, we describe the ability of a 293 packaging cell line to produce retroviral vectors in suspension culture at high titer. Adherent 293GPG cells, producing a Moloney Murine Leukemia Virus (MoMLV) retrovirus vector pseudotyped with the vesicular stomatitis virus G (VSVG) envelope protein and expressing a TK-GFP fusion protein, were adapted to suspension culture in calcium-free DMEM. At a cell density similar to adherent cell culture, the suspension culture produced retroviral vector consistently in the range of 1 x 10(7) infectious viral particles/mL (IVP/mL), with a specific productivity threefold higher than adherent culture. Furthermore, at the same medium replacement frequency, the suspension producer cells could be cultured at higher density than their adherent counterparts, which resulted in virus titer of 3-4 x 10(7) IVP/mL at 11.0 x 10(6) cells/mL. This corresponds to a 10-fold increase in viral concentration compared to adherent cells. The capacity to up scale the retroviral vector production was also demonstrated by performing a 2 VVD perfusion culture for 9 days in a 3L Chemap bioreactor. The combination of suspension and perfusion led to a 20-fold increase in maximum virus productivity compared to the adherent culture.

Acoustics↗
PubMed1995

Rat tail suspension reduces messenger RNA level for growth factors and osteopontin and decreases the osteoblastic differentiation of bone marrow stromal cells.

We previously reported that bone marrow stromal cells produce insulin-like growth factors (IGF-I and -II), and that medium conditioned by marrow stromal cells stimulates osteoblast proliferation in vitro. The present study employed the rat tail-suspension model to unload the hindlimbs. It was designed to test the hypothesis that the development of osteopenia or osteoporosis could be due to a deficit in the osteogenic function of marrow stromal cells. Although tail suspension suppressed body weight during the first 3 days of an 11-day pair-fed study, the overall weight gain recorded by these animals was normal. Nevertheless, bone growth was inhibited by suspension. Similarly, the total adherent marrow stromal cell population harvested from the femurs and tibias was decreased by tail suspension, and only half the normal number of fibroblastic stromal cell colonies grew when they were cultured. The proliferation of alkaline-phosphatase-positive cells in the stroma was also inhibited. Northern hybridization revealed that the messenger RNA level for transforming growth factor-beta 2 and IGF-II in stromal cell was reduced by tail suspension. The production of IGF-II by marrow stromal cells was also decreased. The steady-state level of five different transcript sizes of IGF-I mRNA was altered differentially by tail suspension. Osteopontin mRNA was also reduced in marrow stromal cells from tail-suspended rats compared with the normal rats. These data suggest that skeletal unloading not only alters the mRNA level for growth factors and peptide production, but also affects the proliferation and osteogenic differentiation of marrow stromal cells. These changes may be responsible for the reduced bone formation in osteopenia and osteoporosis.

Animals↗
PubMed1993

Influence of suspension on the expression of protective immunological memory to murine Listeria monocytogenes infection.

Female BDF1 mice were immunized with virulent Listeria monocytogenes, which resulted in the generation of a long-lived state of protective immunological memory for this facultative intracellular bacterial pathogen. The influence of antiorthostatic suspension, a ground-based model employed to simulate certain aspects of weightlessness that occur during spaceflight, on the capacity of these mice to express memory immunity was evaluated. Memory-immune mice were suspended by the tail in the orthostatic or antiorthostatic position and were reinfected with a lethal dose of virulent L. monocytogenes. It was found that suspension did not influence the kinetics of bacterial growth in vivo when the rechallenge infection was started concurrently with the suspension. However, mice that were reinfected on day 2 or 4 of the suspension exhibited an enhanced capacity to eliminate the infection. Attenuation of this enhancing effect was observed when mice were infected on day 7 of the suspension. These results indicate that the stress of antiorthostatic suspension can influence the capacity of the murine host to express protective immunological memory to pathogenic bacteria.

Animals↗
PubMed2001

Transient expression of CYP1A1 in rat epithelial cells cultured in suspension.

Suspension of human epidermal cells in methylcellulose-containing medium induces CYP1A1 by a mechanism requiring functional Ah receptor (AhR). In present work CYP1A1 mRNA was induced in a variety of cultured rat epithelial cells by suspension, but the induction was transient, with CYP1A1 mRNA reaching maximal levels by 5 h and disappearing by 12 h. Though the methylcellulose itself contained no detectable ligand, (a) suspension activated the AhR, as judged by mobility shift assays, (b) the AhR competitive inhibitor alpha-naphthoflavone inhibited suspension-mediated induction, and (c) induction was dependent upon dioxin responsive transcriptional elements in the CYP1A1 promoter. The rapid disappearance of CYP1A1 mRNA after 5 h of suspension was unaffected by the addition of TCDD but was prevented by the inclusion of the protein synthesis inhibitor cycloheximide. Thus the downregulation appears to be mediated by a novel short-lived protein induced or activated by suspension.

Animals↗
PubMedDate not supplied

Adenine nucleotide synthesis in human erythrocytes depends on the mode of supplementation of cell suspension with adenosine.

In suspensions of washed human erythrocytes, adenosine added in a single dose to concentrations of 0.1-10.0 mmol/l suspension was deaminated at rates ranging from 10 to 50 mmol/l cells h. The sum of adenosine, inosine, and hypoxanthine concentrations in the suspension, as well as the intracellular concentration of ATP, remained constant. In the presence of 25-50 mmol/l orthophosphate, addition of a single dose of adenosine into erythrocyte suspension increased the ATP concentration by up to 280% of the initial level. If the initial adenosine concentrations were greater than 5 mmol/l suspension, ATP increased independently of adenosine concentration to the level determined only by the concentration of orthophosphate. After orthophosphate was returned to its initial level, ATP in erythrocytes began to decrease. In the presence of coformycin, erythrocytes utilised adenosine at a rate of 0.2-0.3 mmol/l cells h. Their adenylate pool increased at a rate of 0.10-0.16 mmol/l cells h for several hours, but intracellular ATP increased only slightly. The energy charge of cells decreased significantly from 0.86 +/- 0.05 (control) to 0.82 +/- 0.06. Adenosine continuously pumped into erythrocyte suspensions at rates of 0.02-5.0 mmol/l cells h for several hours caused the adenylate pool of erythrocytes and intracellular ATP to increase synchronously at a rate of 0.02-0.35 mmol/l cells h. The energy charge of these erythrocytes increased significantly up to 0.91 +/- 0.03. After pumping of adenosine was stopped, the intracellular ATP and the adenylate pool began to decrease, returning sometimes to the initial level in 2-3 h.

Adenine Nucleotides↗
PubMed1997

The Effect of Diameter Ratio and Volume Ratio on the Viscosity of Bimodal Suspensions of Polymer Latices

Previously, the rheological properties of different sized monodisperse polymer latices of polystyrene and polymethyl methacrylate (PMMA) were determined. This paper describes procedures in which carefully prepared blends of the same monodisperse latices were mixed together to examine the effect of the differences in size between the latices (diameter ratio) on the rheology of the blend. The relative viscosities of these blends were then measured as a function of the total volume fraction and compared with those of the constituent parts. In a bimodal suspension, theory predicts that a maximum packing fraction and hence a minimum viscosity is achieved with 27% small particles by volume. The experiments revealed that a minimum viscosity was obtained with 25% small particles by volume and with a diameter ratio of 7.83. At this diameter ratio, the small particles are able to pass through the triangular pore between the large particles and this essentially leads to an increased maximum packing fraction of the suspension. Hence the suspension will have a lower viscosity. Other diameter ratios at 25% small particles by volume that led to suspensions with lower viscosities were 4.03, 6.37, and 11.15. On the other hand the suspensions with diameter ratios of 2.81 and 5.67 led to increases in viscosity. This is a result of the small particles being too big to fit in the gaps between the large particles. All the other diameter ratios at all the other compositions (i.e., 50 and 75% small particles by volume) resulted in viscosities higher than that obtained for the monodisperse polystyrene latex. These effects may be explained by changes in the value of the maximum packing fraction. An increased maximum packing fraction of the system leads to lower viscosities and vice versa. The results challenge the conventional view that simply increasing the diameter ratio at a fixed composition leads to reduced viscosities and increased maximum packing fractions. This simple picture does not appear to hold for binary suspensions of colloidal particles at every particle size ratios.

Journal Article↗
PubMed1999

An Analysis of Electrophoresis of Concentrated Suspensions of Colloidal Particles.

An analysis of the electrophoretic motion of charged colloidal particles in a concentrated suspension is developed to predict the electrophoretic mobility of the particles and the electrical conductivity of the suspension. The analysis is based on a unit cell model that takes into account particle-particle hydrodynamic interactions and includes relatively thick electric double layers. The fluid motion in the unit cell is treated by writing the relevant Navier-Stokes equation in terms of the stream function and vorticity. The governing equations were then solved by a finite-difference method. The calculated electrophoretic mobilities are in agreement with prior analytical solutions for moderately concentrated suspensions, and the theory reduces to the result of O'Brien and White for low to moderate zeta potentials and dilute suspensions and to the classical result of Smoluchowski for thin double layers and dilute suspensions. A parametric study shows that the electrical conductivity of the suspension relative to a free electrolyte solution is affected by the counterion to co-ion diffusivity ratio, the double-layer thickness, and the volume fraction of particles. For a dispersion of moderately charged particles (moderate zeta potentials) with thick double layers, the numerical model predicts the electrical conductivity in agreement with experimental values reported in the literature. Copyright 1999 Academic Press.

Journal Article↗