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Physical and microbiological stability of an extemporaneous tacrolimus suspension for paediatric use.

OBJECTIVE: An extemporaneous suspension of tacrolimus for paediatric use has recently been developed but poor bioavailability and erratic plasma concentrations were observed during clinical use. It was not clear whether this was due to changes in the physical properties of the suspension during storage. The aim of this work was to investigate the physical and microbiological stability over the recommended 8-week shelf-life of this extemporaneous tacrolimus suspension. METHODS: Suspensions (0.5 mg/mL) were custom made by a special manufacturer under Good Manufacturing Practice conditions. The procedure involved mixing tacrolimus capsule contents into Ora Plus and Simple Syrup (1 : 1) using a mortar and pestle followed by an homogenization step. The particle sizes of the suspensions were measured using a MasterSizer. A light microscope equipped with polarizers was used to visualize any particle size changes or crystal growth. Viable bacterial and fungal contamination was assessed using standard colony count techniques on solid media. The suspensions were kept at 22-26 degrees C and evaluated weekly. RESULTS: The volume mean diameter d((4,3)) from laser diffraction did not change significantly. Light microscopy did not reveal any significant change in particle size or crystal growth. Contamination by viable and culturable micro-organisms could not be detected. CONCLUSION: The suspension was physically (particle size) and microbiologically stable during the 8-week study period suggesting other factors including poor dosing could be responsible for the pharmacokinetic variation observed during clinical use which warrants further investigation.

Biological Availability↗

Bioavailability of rectally administered carbamazepine suspension in dogs.

The relative bioavailability of an investigational carbamazepine suspension was studied following rectal administration in dogs. Doses of carbamazepine, 20 mg/kg, were given to six dogs. The routes of administration were oral tablet, oral suspension, and rectal suspension. There was no significant difference (p greater than 0.05) in total absorption, as indicated by the area under the serum concentration-time curve between the oral and rectal suspensions. The notable differences between the oral suspension and the rectal suspension were in the maximum serum concentration achieved and the time to achieve this maximum serum concentration. This is due to a prolonged absorption of carbamazepine given rectally, which may limit the ability to achieve therapeutic serum concentrations rapidly. Carbamazepine suspension given rectally may be a satisfactory alternative when administration by the oral route is not possible.

Animals↗

Omeprazole/Antacid-powder suspension-Santarus: omeprazole/sodium bicarbonate powder-Santarus, 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 Acitreltrade mark [SAN 05] and also as Rapinex powder for oral suspension. This omeprazole powder suspension will be used to treat gastrointestinal haemorrhage, gastro-oesophageal reflux disease, heartburn and peptic ulcers. Acitreltrade mark 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 gastrointestinal (GI) diseases. Santarus has licensed exclusive, worldwide rights to patent applications covering specific combination formulations of proton pump inhibitors (PPIs) and antacids for treating various upper GI diseases and disorders. Santarus plans to license the development, distribution and marketing rights of omeprazole powder for oral suspension 20 mg 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 40 mg) with 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 this omeprazole 40 mg powder suspension for an 8-week period. In connection with the NDA for omeprazole powder suspension 40 mg, Santarus provided notice to the NDA holder for Prilosec delayed-release capsules and related patent owners that omeprazole powder suspension 40 mg does not infringe currently listed patents for Prilosec or that those patents are invalid.

Antacids↗

Pre-cultivation in suspension obtained chondrocyte-enriched cultures from articular-epiphyseal cartilage in fetal rats.

To establish a reliable chondrocyte culture system is valuable for investigating the phenotypic properties or the drug effects on chondrocytes. In this study, we established a chondrocyte-enriched culture system by pre-cultivating cells isolated from fetal rat articular and epiphyseal cartilage in suspension prior to cultivating in monolayer. Our results showed that the cultures with 5 days of preculture in liquid suspension produced the highest chondrocyte representative matrix of sulfated glycosaminoglycan compared to those with 1 or 3 days in suspension. We also found that PGE2 (10 and 100 nM) effects on DNA synthesis showed biphasically in 1 day-suspension chondrocyte cultures, similar to those of fibroblast cultures, while PGE2 (1-100 nM) revealed suppressive effects on DNA synthesis in 3 day-suspension chondrocyte cultures, similar to those of osteoblast cultures. However, PGE2 (0.1-100 nM) had no significant effects on the DNA synthesis of 5 days-suspension chondrocyte cultures. These results suggest that the monolayer chondrocyte culture following 5 days of suspension may be a reliable method to exclude the contaminated cells and obtain the chondrocyte-enriched cultures. In this study, we also found that 24-hour treatment of PGE1 (100-1000 nM), but not PGE2 or PGF2 alpha, revealed inhibitory effects on DNA synthesis in chondrocyte-enriched cultures. These phenomena may be as markers to check the characteristics of chondrocyte cultures derived from rat articular and epiphyseal cartilage, and also provide the information for further investigation about chondrocytic functions.

Animals↗

Effects of estrogen on tail suspension-induced disuse atrophy in ovariectomized rats: evaluation of the expression of interleukin-6 mRNA in the femur.

It is known that estrogen deficiency results in osteoporosis in human and experimental animals. However, how this deficiency affects the development of disuse bone atrophy is not well understood. Recently, it has been reported that estrogen affects the production of cytokines such as interleukin 6 (IL-6) which acts as local bone-resorbing factor. We thus studied how estrogen deficiency caused by ovariectomy and estrogen supplements affects the expression of IL-6 mRNA in the femur of tail-suspended rats. Five-week old female Wistar rats were ovariectomized and divided into two groups. One group received an intramuscular injection of estradiol dipropionate once a week (OVX-E2 group), and the other received the vehicle alone (OVX group). After the third injection, the rats were subjected to tail suspension in metabolic cages for 1, 3, 5 and 7 days. The wet weight of femurs significantly decreased after day 3 of tail-suspension in the OVX group. However, no significant decrease was observed in the OVX-E2 group. The expression of IL-6 mRNA estimated by RT-PCR (reverse transcription coupled polymerase chain reaction) in the femur significantly increased on day 5 after tail suspension in the OVX group. In the OVX-E2 group, that level significantly decreased on day 1 after the commencement of tail suspension. During suspension the level tended to be lower than that in the OVX group, a significant difference being observed on days 5 and 7 of suspension. The present results suggest that estrogen administration to OVX rats prevents both IL-6 production in the femur and the development of disuse bone atrophy induced by tail suspension.

Animals↗

Effect of suspending agents on the characteristics of some anti-inflammatory suspensions.

The effect of suspending agents on the physical stability and in vitro availability of mefenamic acid, flufenamic acid, glafenine, ibuprofen and azapropazone suspensions was studied. The ulcerogenic effect of these formulated suspensions on the stomach of rats was also investigated. The results revealed that 2% veegum and 2% sorbitol gave the best formulated suspension for glafenine as compared to other formulations. On the other hand, 2% veegum, 2% sobitol and 1% avicel was found to improve the physical stability of mefenamic acid and flufenamic acid suspensions. Also, the combination of 1% veegum, 1% sorbitol and 1% algin produced excellent suspension for ibuprofen and azapropazone as compared to other combinations. The results of in vitro release data proved an optimal availability of the above mentioned formulations. In addition, significant reduction in the gastric erosions in stomach of rats was observed in all mentioned suspensions except glafenine suspension.

Animals↗

[The relative bioavailability of co-trimoxazole suspensions].

The relative bioavailability of a co-trimoxazole suspension manufactured by VEB Berlin-Chemie (B); Belocid-Suspension was compared with a widespread used suspension (V) in healthy male students (22-29 ys. aged). A single oral dose of 160 mg trimethoprim (TPM) and 800 mg sulphamethoxazole (SMZ) produced similar blood levels with either preparation. The TMP peak levels were 1.44 +/- 0.18 (B) and 1.40 +/- 0.26 mg/l (V), respectively after 1.5 and 1.0 h on an average. The AUC amounted to 18.94 +/- 2.25 (B) and 17.19 +/- 3.62 mg . h/l (V), respectively. About one half (52.5%) of the given TMP dose was excreted unchanged by kidney within 48 h after administration of the respective suspension. The SMZ peak levels run to 37.2 +/- 10.3 (B) and 38.6 +/- 5.4 mg/l (V) after 3.6 +/- 3.5 and 1.3 +/- 0.8 h. The AUC were identical: 682.3 +/- 126.2 (B) vs. 686.9 +/- 165.8 mg . h/l (V). After both preparations 67% of the given SMZ dose could be detected in urine within 48 h. In two out of the eight volunteers the absorption of B was delayed, but it passed off to the same extent. In all other cases absorption of the suspension was accelerated in comparison with tablet administration studies reported. Peak blood levels of TMP and SMZ after ingestion of the suspensions reach the lower range of values resulting from tablet intake. Both suspensions are regarded interchangeable with respect to bioavailability, which is also comparable to co-trimoxazole tablets.

Adult↗

[Optical density changes in bacterial protoplast suspensions exposed to membrane-active antibiotics].

The effect of membrane active antibiotics, such as gramicidin S, its derivatives and carbonyl-conjugated pentaens on suspended bacterial protoplasts resulted in lysis of the protoplasts accompanied by a marked decrease in the optical density (OD) of the suspensions. However, when the drug concentrations were lower than those inducing the lysis, an increase in the suspension OD by 10-30 per cent as compared to the control values of the OD was often observed. The increase in the protoplast suspension OD was most pronounced with the use of the drugs with a relatively low lytic activity or under the conditions lowering the lytic activity of the antibiotics. Under such conditions no agglutination of the protoplasts was observed. The comparative estimation of the protoplast diameters by the method of Klenin et al. in the control suspensions of M. lysodeikticus protoplasts and in the suspensions with a stable increase in the OD showed that the OD increase was associated with swelling of the protoplasts: an increase in the suspension OD by approximately 30 per cent corresponded to an increase in the protoplast diameter by approximately 15 per cent. The observed increasing of the suspension OD must be due to the fact that the membrane active antibiotics induced a decrease in the osmotic stability of the protoplasts not sufficient for their lysis.

Anti-Bacterial Agents↗

Stability of extemporaneous suspensions of carbamazepine.

The stability of carbamazepine in four suspending vehicles is reported. Suspensions of carbamazepine 200 mg/5 ml in sorbitol 70%, simple syrup, modified Hospital of the University of Pennsylvania Suspending Vehicle (HUP), and diluted HUP (HUP-A) were prepared. The first three suspensions were stored in amber glass bottles and oral syringes at 4, 25, and 37 degrees C, and the HUP-A suspension was stored at 4 degrees C. Physical stability was assessed by visual inspection of sedimentation, ease of pouring, and foaming upon shaking. Carbamazepine concentrations were determined periodically over 90 days by an enzyme-multiplied immunoassay. The assay was validated by acid-heat degradation of the drug, separation of breakdown products by thin-layer chromatography, and confirmation of non-reactivity of the breakdown products with the assay. The concentration of carbamazepine in sorbitol 70%, simple syrup, and HUP-A was at least 90% of the prepared concentration at all sampling times. Although separation occurred, the simple syrup suspensions could be redispersed. The suspension in HUP-A remained homogeneous, was easy to pour, and produced less foam than the HUP suspension. Extemporaneously compounded suspensions of carbamazepine in HUP-A or in simple syrup can be used for patients who require a liquid dosage form. Even though sorbitol 70% produced a pharmaceutically acceptable product, its use is not recommended because it has been reported to cause intractable diarrhea.

Carbamazepine↗

Testing automated liquid-based cytology samples with a manual liquid-based cytology method using residual cell suspensions from 500 ThinPrep cases.

We report a technical improvement upon a previously disclosed manual liquid-based cytology (MLBC) method; and, we use the improved method to prepare slides from residual ThinPrep specimens in order to see how often ThinPrep diagnoses correspond to diagnoses derived from exhaustive examination of their parent sample suspensions. Residual cell suspensions from 500 ThinPrep cases comprising (1) 20 low-grade squamous intraepithelial lesions (LSILs); (2) 200 high risk (HR) negatives and 20 ASC-US; and (3) 260 screening cytology specimens were studied. Institutional review committee guidelines allowed us to know diagnoses by groups of specimens, but did not allow us to know individual patient diagnoses, so we could not perform case-by-case matched outcome-comparisons. Cells were concentrated by conventional centrifugation and sedimented into a polymer gel that was then vortex-mixed and converted into a viscous cell-rich suspension. The cell suspension was smeared between two clean glass slides, which were air-dried and stained with the Papanicolaou stain. Two study-sets were created, comprising one slide from each case. Each of the two study sets was examined by two cytopathologists, and discordant diagnoses were adjudicated. Because of the ambiguity involved in the "atypical" (ASC-US, ASC-H, AGC) diagnosis categories, only outcomes at the level of LSIL or greater were recorded. All MLBC SILs were digitally imaged and abnormal slides plus digital images were sent to the laboratory that provided the residual automated liquid-based cytology (ALBC) suspensions. The final diagnoses were confirmed by the laboratory that provided the residual ALBC specimens. MLBC slides of the 20 LSIL cases afforded 2 high-grade squamous intraepithelial lesions (HSILs) and 18 LSILs. Those of the 200 HR-Negatives showed 3 HSILs and 30 LSILs; and those of the 20 HR-ASC-US showed 3 HSILs and 9 LSILs. MLBC slides of the 260 screening cytology specimens showed 1 Carcinoma, 3 HSILs and 20 LSILs; affording 3 HSILs and 14 LSILs more than originally diagnosed. The MLBC method of this report is useful for preparing cell suspensions for cytological examination. Our analytical method was exhaustive and used nearly all of the cell material that was provided to us for analysis; therefore, we conclude that this approach is useful for determining how well ALBC instruments represent their parent sample suspensions. It appears that "rare events" may be overlooked when limited sample aliquots are analyzed by ALBC instruments, and this probably accounts for our increased discovery of SILs by the MLBC method. Also, SILs often present as aggregates of cohesive cells which, if overlooked or ineffectively transferred to ALBC slides, would not be diagnosed.

Cytological Techniques↗

Rheological Properties of Aqueous Suspensions of Chitin Crystallites

Rheologically, suspensions of chitin crystallites are found to behave as other molecular liquid crystalline polymers (LCPs). The average hydrodynamic diameter of the crystallites in the suspension at pH 4 is determined to be approximately 80 nm using dynamic light scattering. Conductimetric and pH titration results show that the pKa of the crystallites is 6.3, which is the same as that reported for chitosan. In combination with phase diagrams, flow properties of isotropic, biphasic, and anisotropic chitin suspensions were investigated. For isotropic suspensions, a classical shear thinning behavior of rodlike particles is observed. In the case of biphasic suspensions, a two-regime curve is observed where tactoids first orient, deform, and then break up under a shearing force. Similar to other LCPs, a three-regime flow curve is found for the anisotropic suspensions. The viscosity-concentration curve exhibits a maximum at the phase separation concentration, and this maximum is less distinct with a decrease of the ionic strength. Secondary electroviscous effects due to strong particle-particle interactions influence the viscosity of the suspensions at higher concentrations.

Journal Article↗

Role of Electrostatic Repulsion on the Viscosity of Bidisperse Silica Suspensions.

The flow behavior of bidisperse aqueous silica suspensions has been studied at different electrolyte concentrations as a function of shear rate, total volume fraction of the particles, and volume ratio of small to large particles. It is shown that the range of the electrostatic repulsion plays an important role in determining the viscosity of the suspension. Binary mixtures of particles of longer range repulsive forces showed higher viscosities than the suspensions of shorter range electrostatic interactions. Bimodal suspensions of long-range interactions showed non-Newtonian behavior over wider ranges of shear due to the deformation of the ionic cloud around the particles, which is larger in these systems. The viscosity of bimodal suspensions used in this study was scaled with respect to the viscosity of the related monosized systems and the viscosity of one bimodal suspension at a fixed total volume fraction of the particles, employing our earlier scaling method. The model normalizes the effect of colloidal forces by introducing a scaling factor that collapses the data into a single curve for bimodal suspensions of a particular size ratio, and it is shown that the model is valid for systems with both short-range and long-range repulsive forces. Copyright 1999 Academic Press.

Journal Article↗

Ethionine toxicity in vitro: the correlation of data from rat hepatocyte suspensions and monolayers with in vivo observations.

The hepato-steatogenic compound ethionine has been used to investigate the correlations between in vivo and in vitro toxicity data. The aim was to find a suitable model of toxicity in hepatocyte suspensions or monolayers in vitro, which could predict the known toxicity of ethionine in vivo and which could be implemented in screening compounds of unknown toxicity. Thus a variety of markers of cytotoxicity, metabolic competence and liver-specific functions were investigated in rat hepatocyte suspensions and monolayers and compared with in vivo data in the rat. The following markers were measured in the appropriate system: (1) Neutral red uptake; 3-(4,5 dimethyl)thiazol-2-yl,-2,5-diphenyl tetrazolium bromide (MTT) reduction; lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) leakage (cytotoxicity). (2) ATP levels, protein synthesis and glutathione (GSH) levels (metabolic competence). (3) Urea and triglyceride synthesis and beta-oxidation (liver specific functions). Ethionine (0-30 mM) did not affect the markers of direct cytotoxicity, except neutral red uptake, which was reduced by 18 and 30 mM ethionine after 20 h in culture. ATP and GSH depletion occurred in hepatocyte suspensions at the highest concentrations of ethionine (20 and 30 mM) after 1 h. In monolayers, GSH levels were reduced after 4 h, but not 20 h. Urea synthesis was increased in hepatocyte suspensions from 1 to 3 h by 10-30 mM ethionine and reduced after 20 h in cultured hepatocytes (18-30 mM). Protein synthesis was reduced and beta-oxidation was increased in ethionine-treated hepatocyte suspensions. Unfortunately, there was no measurable effect on triglyceride accumulation within cells (the major biochemical change in vivo) in either system. Ethionine treated hepatocytes in suspension showed the same rate of triglyceride synthesis and transportation out of cells as control cells. Thus, hepatocyte suspensions were able to mimic the early biochemical effects of ethionine in vivo (ATP and GSH depletion, inhibition of protein synthesis) and some effects on urea synthesis, but monolayer cultures appeared to be less sensitive to the toxicity of ethionine. However, neither in vitro system was able to model the effects of ethionine on the accumulation of triglycerides in vivo.

Adenosine Triphosphate↗

Effect of bilateral in vivo ischemia/reperfusion on the activities of superoxide dismutase and catalase: response to a standardized grape suspension.

PURPOSE: Ischemia/reperfusion (I/R) is a major etiological factor in the bladder dysfunctions observed in men with lower tract obstruction, women with postmenopausal incontinence and with aging. A standardized grape suspension protects the rabbit urinary bladder from both the contractile dysfunctions and the morphologic changes mediated by I/R. Using a model of in vivo bilateral ischemia/reperfusion, the current study investigated the effect of this grape suspension on the endogenous antioxidant defense systems. MATERIALS AND METHODS: 24 NZW rabbits were separated into 6 groups of 4. Groups 1-3 were treated by gavage with aqueous grape suspensions; groups 4-6 received sugar-water vehicle. Groups 3 and 6 were controls. Groups 1 and 4 were subjected to bilateral ischemia for 2 h (I). Groups 2 and 5 underwent bilateral ischemia for 2 h and reperfusion for 1 week (I/R). For all rabbit bladders, the muscle and mucosa were separated by blunt dissection and analyzed separately. The effects of the various treatments on bladder antioxidant systems of cytoplasmic superoxide dismutase (Cu-Zn superoxide dismutase; SOD), and catalase (CAT) were evaluated. RESULTS: The standardized grape suspension up-regulated both SOD and CAT activity of bladder muscle and mucosa in control animals. There were few differences in the grape suspension treated animals after ischemia, and in general the activities decreased following I/R. CONCLUSIONS: Increases of SOD and CAT activity in control animals as a result of grape suspension suggest a greater antioxidant capacity. This increase in the antioxidant defense system may explain the increased protection of grape suspension in the face of ischemia and I/R. However, the activities of both enzyme systems decreased in the smooth muscle subjected to I/R showing that reperfusion damages these systems probably via oxidation damage to the enzymes themselves.

Animals↗

Angiogenesis and the blood-brain barrier in intracerebral solid and cell suspension grafts.

Solid and suspension grafts of fetal central nervous system (CNS) tissue rapidly reform an intact blood-brain barrier (BBB), whereas solid grafts of peripheral nervous system (PNS) tissue fail to establish a BBB as detected by horseradish peroxide (HRP) leakage, administrated intravenously. We examined the acute changes in the BBB after grafting of fetal CNS tissue in solid and suspension form and superior cervical ganglion (SCG) and PNS tissue in the same manner. Adult rats (n = 20) received fetal (day 14-15) forebrain grafts (either solid or cell suspension) to their rostral corpus callosum bilaterally. A second group (n = 20) received SCG solid and cell suspension grafts at the same coordinates with the same technique. The animals were killed on first, third, seventh, and tenth days after grafting. Intravenous HRP (Sigma, type VI, 75 mg/5-g rat) was given 1 hour before perfusion with mixed aldehydes. Fifty-micron coronal sections were examined for the presence and location of the graft by cresyl violet and AChE staining and Mesulam's TMB method to detect HRP leakage. HRP leakage was detected in the parenchyma in all groups on the first and the third days post-transplantation indicating a disrupted BBB. No HRP reaction was seen at days 7 and 10 in groups receiving fetal forebrain tissue whether solid or cell suspension. Solid grafts of SCG consistently demonstrated HRP leakage from the first through the tenth day. However, cell suspension of SCG established a BBB by 7 days. These results suggest that within the solid grafts of CNS and PNS tissue, the permeability of the vessels is dictated by the transplanted tissue itself. When cell suspensions of the same tissue are introduced, host CNS tissue dominates as the local environment resulting in non-leaky vasculature within the graft.

Animals↗

Fatigue testing of selected suspension manual wheelchairs using ANSI/RESNA standards.

OBJECTIVES: To evaluate the durability and value of 3 common suspension manual wheelchairs and to compare the results with those of previously tested lightweight and ultra-lightweight folding-frame wheelchairs. DESIGN: Standardized fatigue testing and cost analysis of 3 suspension manual wheelchairs from 3 different manufacturers. SETTING: A rehabilitation engineering center. SPECIMENS: Nine suspension manual wheelchairs. INTERVENTIONS: Wheelchairs were fitted with a standardized wheelchair test dummy and tested on a series of fatigue tests, consistent with those developed by the International Organization for Standardization. Main outcome measures Fatigue life (measured as the number of equivalent cycles completed) and value (equivalent cycles divided by cost) were compared among all wheelchairs. RESULTS: Analysis of variance revealed significant differences (P< or =.05) in the number of equivalent cycles among the suspension wheelchairs tested. When compared with previously tested ultra-lightweight and lightweight wheelchairs, the suspension wheelchairs failed to show significant improvements; however, significant improvements were found between individual suspension and lightweight wheelchairs. CONCLUSIONS: We found little evidence to suggest that suspension manual wheelchairs provide advantages in terms of durability or value over standard lightweight and ultra-lightweight folding-frame wheelchairs.

Equipment Design↗

Primary stability of hamstring graft fixation with biodegradable suspension versus interference screws.

PURPOSE: During the early postoperative period, the stability of the fixation of a hamstring graft to the bone tunnel is the primary factor in limiting rehabilitation. The aim of this study was to evaluate if the initial fixation strength of a new suspension screw is comparable to that of the biodegradable interference screw fixation technique in the hamstring reconstruction of the anterior cruciate ligament (ACL). TYPE OF STUDY: Experimental laboratory study. METHODS: We evaluated the initial fixation strength of a biodegradable poly-L-lactide/tri-calcium phosphate (PLLA/TCP) screw that suspended the graft in the bone tunnel and compared it with the strength of an interference screw for fixation of hamstring grafts in ACL reconstruction using bovine knees. Single-cycle and cyclic loading tests were performed using a materials testing machine. RESULTS: The suspension screw provided a significantly higher yield load and ultimate failure load than the interference screw. There was no significant difference in the stiffness of both techniques. The typical failure mode for the suspension screw was fracture of the screw and for the interference screw it was slippage of the graft past the screw. In cyclic testing, both methods of fixation ran out to 1,000 cycles up to 250 N with a mean displacement of 2.6 mm (range, 1.8 to 3.3 mm) for the suspension screw and 4.1 mm (range, 2.3 to 6.0 mm) for the interference screw. Only the grafts fixed with the suspension screw survived a protocol with 1,000 cycles up to 400 N. CONCLUSIONS: Our biomechanical data suggest that hamstring graft fixation using a biodegradable PLLA/TCP suspension screw provides an alternative to interference screw fixation. CLINICAL RELEVANCE: Hamstring graft fixation using a suspension screw provides a reasonable alternative to interference screw fixation.

Absorbable Implants↗

Preparation of stable aqueous suspension of a hydrophobic drug with polymers.

Pharmaceutical preparation of a hydrophobic aldose reductase inhibitor 5-(3-ethoxy-4-pentyloxyphenyl)-2,4-thiazolidinedione (CT112) was investigated. CT112 dissolved in a basic solution with different kinds of polymers was neutralized by acid to obtain a suspension preparation. In particular, the addition of a polymer, hydroxypropyl methyl cellulose (HPMC) provided a stable CT112 suspension with a homogeneous particle size, and there seemed to be an optimal concentration of HPMC for the stable suspension. The addition of polysorbate 80 brought higher CT112 solubility in water, but did not provide a stable suspension. X-ray diffraction, IR spectrum, and thermal analysis revealed that the particles in the suspension with HPMC had lower degree of crystallinity, less hydrophobic particle surface, and lower melting point and decreased fusion enthalpy than the suspension without HPMC. These results suggested that the highly stable CT112 suspension could be attained by the adsorption of the polymer.

Cellulose↗