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[Resorbable staple sutures for partial stomach and duodenal stump closure. Animal experiment studies].

In two groups of pigs, 10 in each, partial gastrectomies with gastroduodenostomy (Billroth I) respectively gastrojejunostomy (Roux-en-Y) were performed. Absorbable lactomer (Polysorb, Auto-Suture) staple lines--a copolymer of glycolic acid/lactic acid-, used for the closure of the lesser curvature of the stomach and the duodenal stump, were safe. No suture dehiscence was observed. Macroscopic examination showed no major inflammatory adhesions around the staples. Microscopically inflammatory reactions around the staples in the gastrointestinal wall were found. Our results yielded no contraindication for clinical tests of absorbable sutures in gastrointestinal surgery.

Anastomosis, Roux-en-Y↗

The use of d-limonene preparation as a dissolving agent of gallstones.

The dissolving mixture is administered through a choledochal drain to treat postoperatively retained cholesterol gallstones. It is prepared by mixing 97.0 parts of d-limonene with 2.1 parts of polysorbate 80 and 0.9 part of sorbitan monooleate, a mixture of which may easily reach the surface of the gallstones which are wetted by bile. The d-limonene preparation was found to be safe both in laboratory experiments and clinical trials. Before applying the preparation, the usual choledochal drain must be replaced with a recently developed catheter made from epichlorohydrine rubber, which is chemically resistant to the preparation. Three cases of retained gallstones are described where the preparation was successfully used. In the fourth case treatment with the preparation was tried in lieu of surgery but was not successful due to other complications. However, some dissolution of retained stones was observed. There were no postoperative complaints in the long-term follow-up of some cases for more than 2 yr after treatment with the preparation. This procedure promises to be of value because retained cholesterol stones may be dissolved without the necessity of further surgery.

Adult↗

Influence of two-dimensional and three-dimensional imaging on endoscopic bowel suturing.

Several three-dimensional (3-D) video-endoscopic systems have been introduced in surgical practice to enhance depth perception during minimal access surgery (MAS), but the facilitation of endoscopic manipulations by the current 3-D systems remains unproved. The aim of the study was to investigate the influence of 2-D and 3-D imaging modalities on intracorporeal suturing. The standard task consisted of suture closure of 60 mm enterotomies made in porcine small bowel with continuous seromuscular 3/0 Polysorb. Ten experienced surgeons participated in the study. The imaging systems were Storz (2-D), Welch Allyn (3-D), and Zeiss (as both 2-D and 3-D). Each surgeon performed two tasks with each modality in a random sequence. The outcome measures were execution time, suture line leakage pressure, and suture placement score. In addition, the participating surgeons assigned subjective scores on the image quality and the adverse effects of the imaging systems. There was no significant difference in the execution time, leakage pressure, and suture placement score among the various imaging modalities. Depth perception was rated as similar with 2-D and 3-D imaging. Surgeons experienced visual strain with the three systems, but it was rated higher with 3-D imaging. With the current technology, we have not documented any significant difference in task efficiency and quality of endoscopic bowel suturing by trained surgeons between 2-D and 3-D imaging systems.

Analysis of Variance↗

Safe closure technique for distal pancreatic resection.

BACKGROUND AND AIMS: Various methods had previously been employed to manage the proximal pancreas after distal resection (mattress sutures with duct ligation; pancreato-enterostomy or stapling with stainless steel staples, etc.), with postoperative complications in 13% (6%-30%) of the cases, on average. In our practice, to reduce these complications, we applied staples made from Polysorb (Auto Suture), an absorbable lactomer. PATIENTS/METHODS: In the past 10 years, distal pancreatic resection in 90 patients [62 men, 28 women, mean age 52 (24-72)] years) was followed by closure of the resection surfaces with absorbable lactomer clips. Indications for distal resection (with or without splenectomy) were: focal pancreatic necrosis, spontaneous pancreatic fistulas, abscess, pseudocyst, traumatic disruption, segmental chronic obstructive pancreatitis in the tail, and benign (cystadenoma, or insulinoma) or malignant tumours. RESULTS: The postoperative period was uneventful in all these patients, without any complications (pancreatic fistula, abscess or bleeding). No morbidity or mortality occurred in the follow-up period (6 or 12 months postoperatively) with the exception of one patient who suffered a pseudocyst 6 months after surgery and was treated by cysto-jejunostomy. CONCLUSIONS: The clinical results clearly demonstrated that the application of absorbable lactomer staples for closure of the transected margin of the pancreas is a safe alternative to the standard closure technique. These staples can be applied in all cases when distal pancreatic resection is indicated for benign or malignant disorders or a traumatically injured pancreatic gland.

Absorbable Implants↗

VersaStep trocar hernia rate in unclosed fascial defects in bariatric patients.

OBJECTIVE: Use of the VersaStep trocar system (US Surgical, Norwalk, CT) has the perceived advantage of minimal trocar-related hernias in patients undergoing Roux-en-Y gastric bypass surgery (RYGB). We performed a retrospective review of our last 747 consecutive operative procedures using these trocars. METHODS AND PROCEDURES: The patient population was 747 consecutive patients who underwent laparoscopic RYGB at Duke University Health System Weight Loss Surgery Center from January 2002 through April 2005. A total of 3735 radially expanded trocar sites were used. VersaStep trocars were used in all cases. The port configuration included one supraumbilical Hasson port, two 12-mm ports, and three 5-mm ports. The Hasson port was closed with a figure-of-eight number 1 Polysorb suture. All other trocar sites had no fascial closure. Intestinal anastomoses were created with a linear stapler in all of the laparoscopic cases, with hand suturing of the residual enterotomy. The fascial incisions were therefore not extended to accommodate an EEA stapler. The charts were reviewed for occurrence of subsequent trocar site hernias. RESULTS: There were no hernias at any of the VersaStep trocar sites-an incidence of 0%. There were nine incisional hernias at the Hasson port site which later required surgical repair-an incidence of 1.20%. CONCLUSIONS: There were no hernias detected at any of the 1494 12-mm or 2241 5-mm VersaStep trocar sites, despite lack of suture closure. At the Hasson port site, there was a hernia incidence of 1.20%. In the bariatric RYGB population, routine suture closure of the fascia or muscle is not necessary when using radially expanding VersaStep trocars.

Anastomosis, Roux-en-Y↗

Comparative effects of rapid bolus administration of aqueous amiodarone versus 10-minute cordarone I.v. infusion on mean arterial blood pressure in conscious dogs.

OBJECTIVE: This study was designed to test the hypothesis that rapid bolus administration of an aqueous formulation of intravenous amiodarone causes less hypotension than a 10-minute infusion of the standard formulation, Cordarone IV. Hypotension was the most common adverse event reported with Cordarone IV. The hypotension was not dose related, but related to the rate of infusion. Therefore, product labeling calls Cordarone and its generic formulations to be administered over 10 minutes. Cordarone IV contains polysorbate 80 and benzyl alcohol, each causes hypotension. A new aqueous formulation of amiodarone (Amio-Aqueous) does not contain these agents and therefore may cause less hypotension. METHODS: Six conscious beagle dogs were instrumented with a telemetric device for blood pressure monitoring. The study was conducted on 5 days. On the first 2 days, a 10-min infusion or a bolus of D(5)W was administered (placebo). Over the following 3 days, the dogs received (in randomized order, one per day) a 10-min infusion of 2.5 mg/kg Cordarone IV and boluses of 2.5 mg/kg and 5.0 mg/kg Amio-Aqueous injected over 2 to 5 sec. The dogs were monitored for 2 hrs after dosing. RESULTS: Compared to placebo, boluses of aqueous amiodarone produced no significant changes in the mean arterial blood pressure (MABP). In contrast, Cordarone infusion produced significant decreases in MABP that lasted for at least 2 hrs (p < 0.001). CONCLUSION: Amio-Aqueous had significantly better hemodynamic profile permitting rapid intravenous administration. This is a significant advantage over the standard formulation, because Cordarone cannot be administered by rapid bolus due to excipient-related hypotension.

Amiodarone↗

Agents for gallstone dissolution.

Numerous methods are presently available for gallstone dissolution, including oral bile salts; cholesterol solvents such as mono-octanoin and methyl tert-butyl ether; calcium or pigment solvents such as EDTA and polysorbate; mechanical extraction techniques through a T-tube tract or after endoscopic sphincterotomy; or fragmentation methods such as ultrasonography or electrohydraulic lithotripsy, lasers, and extracorporeal shock waves. Which, if any, of these methods will be appropriate for an individual patient depends on the type of stones, whether they are in the gallbladder or bile ducts, whether access to the biliary tree is available, the patient's age and general medical condition, and the availability of expert radiologists, endoscopists, and newer equipment. In the United States, the only available oral bile salt for cholesterol gallstone dissolution is chenodeoxycholate. Ursodeoxycholate, which is more rapid and less toxic, has not been approved by the Federal Drug Administration. These agents are most effective in thin women with small, floating, radiolucent cholesterol gallstones in a functioning gallbladder. Only about half of this small subset of patients, however, will experience partial or complete dissolution of stones in 6 to 12 months. Moreover, recurrence is very likely, and the potential toxicity of long-term therapy is unknown. Thus, for most patients, cholecystectomy remains the most cost-effective and, perhaps, safest option. Intragallbladder instillation of methyl tert-butyl ether and extracorporeal shock wave therapy are also likely to be applicable to only small subsets of patients and to be associated with high recurrence rates. In patients with retained ductal cholesterol stones and access to the biliary tree, mono-octanoin therapy is advantageous in that it can be begun as soon as cholangiography demonstrates no extravasation. In properly selected patients, a 90 percent success rate with mono-octanoin infusion can be expected within a week. Radiologic or endoscopic extraction techniques require maturation of a relatively straight T-tube tract but are not dependent on the type of stone. In the hands of experts, these techniques are highly successful. In postcholecystectomy patients without access to the biliary tree, endoscopic sphincterotomy has become the preferred method of management and can be expected to succeed in more than 90 percent of patients. At this point, the exact role for ultrasonic or electrohydraulic lithotripsy and lasers is unknown. However, these techniques may be applicable in the future in patients with retained bile duct stones in whom extraction and infusion techniques have failed.

Administration, Topical↗

Study of antireflux nipple valves of Kock ileal urinary reservoir. Experimental investigation in dogs.

To better assess the construction, maintenance, and function of the Kock ileal urinary reservoir with its continent antirefluxing nipple valves, laboratory investigations in dogs were done simultaneously with clinical trials in humans in 1983. Fifteen dogs underwent creation of hemi-Kock ileal reservoirs (without the efferent valve and limb) that were anastomosed to their bladders as enterocystoplasties. The afferent antirefluxing nipple valves were intussuscepted after 7 cm of underlying mesentery had been removed. The nipples were further stabilized with metal and absorbable (Polysorb) staples and Marlex collars. The right ureters were anastomosed to the afferent limb of the reservoirs with the contralateral systems left intact as controls. Ten dogs were able to be followed at the vivaria for twelve to thirty-six months and then studied. All nipple valves remained intact, viable, and nonrefluxing without revision. All kidneys remained histologically normal except those in dogs with dilated ureters secondary to ureteroileal stenosis with concurrent calculi formation. Calculi formed on exposed metal staples and Marlex. The absorbable staples were found to promote appropriate healing and were never the nidus for stone formation. It appears that the intussuscepted nipple valve (with its mesentery removed) is reproducible and functionally reliable in preventing reflux. It also appears these valves can histologically preserve diverted kidneys if the upper urinary tract drainage is normal and calculi are minimized. The proper placement of staples and the elimination of Marlex-anchoring collars are indicated to minimize calculi.

Anastomosis, Surgical↗

Inhibition of the ocular effects of sodium arachidonate by anti-inflammatory compounds.

Topical administration of aqueous solutions of sodium arachidonate to the eyes of rabbits increases intraocular pressure, constricts the pupil and increases both the protein and prostaglandin content of aqueous humor. Arachidonic acid itself dissolved in arachis oil is less effective than sodium arachidonate, although addition of polysorbate mono-oleate greatly increases the effects produced by arachidonic acid. Pretreatment with topically applied non-steroidal anti-inflammatory agents prevents the ocular effects of sodium arachidonate, indomethacin being 2-4 times as potent as either indoxole or pirprofen. Dexamethasone was without effect in these experiments. The results suggested that nonsteroidal anti-inflammatory agents deserve serious consideration for topical use in the treatment of ocular inflammation.

Administration, Topical↗

Micellar acid-base potentiometric titrations of weak acidic and/or insoluble drugs.

The effect of various surfactants [the cationics cetyl trimethyl ammonium bromide (CTAB) and cetyl pyridinium chloride (CPC), the anionic sodium dodecyl sulphate (SDS), and the nonionic polysorbate 80 (Tween 80)] on the solubility and ionization constant of some sparingly soluble weak acids of pharmaceutical interest was studied. Benzoic acid (and its 3-methyl-, 3-nitro-, and 4-tert-butyl-derivatives), acetylsalicylic acid, naproxen and iopanoic acid were chosen as model examples. Precise and accurate acid-base titrations in micellar systems were made feasible using a microcomputer-controlled titrator. The response curve, response time and potential drift of the glass electrode in the micellar systems were examined. The cationics CTAB and CPC were found to increase considerably the ionization constant of the weak acids (delta pKa ranged from -0.21 to -3.57), while the anionic SDS showed negligible effect and the nonionic Tween 80 generally decreased the ionization constants. The solubility of the acids in aqueous micellar and acidified micellar solutions was studied spectrophotometrically and it was found increased in all cases. Acetylsalicylic acid, naproxen, benzoic acid and iopanoic acid could be easily determined in raw material and some of them in pharmaceutical preparations by direct titration in CTAB-micellar system instead of using the traditional non-aqueous or back titrimetry. Precisions of 0.3-4.3% RSD and good correlation with the official tedious methods were obtained. The interference study of some excipients showed that a preliminary test should be carried out before the assay of formulations.

Acids↗

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↗

Using highly carboxylated microspheres to simplify immunoassays and enhance diffusional mixing in a microfluidic device.

Manufacturers of latex immunoassays have typically added surfactants to improve detection sensitivity and prevent non-specific aggregation of microspheres, which may cause both false positives and negatives during diagnostic testing. There is also growing interest in conducting immunoassays in smaller volumes using microfluidic devices with minimum human effort. The first goal of our study was to simplify immunoassays by eliminating the use of surfactants. Our second objective was to determine if this strategy would also enhance diffusional mixing in a microfluidic channel, which has been one of the biggest barriers to using these devices. We first ran a series of cuvette experiments to document the performance of sodium dodecyl sulfate (SDS) and polysorbate 80 (Tween 80) surfactants in a mouse immunoglobulin G (IgG) immunoassay using plain polystyrene microspheres. Next, we tested highly carboxylated microspheres with no surfactants, to determine if the same levels of accuracy and specificity could be achieved. Finally, we evaluated the surfactants and highly carboxylated microspheres in a microfluidic device. Our results show that highly carboxylated microspheres can indeed be used to replace surfactants and to induce rapid mixing via diffusion in a microfluidic device.

Carboxylic Acids↗

Single dose and multiple dose studies of itraconazole nanoparticles.

The objective of this study was to determine and compare the lung and serum concentrations in mice following oral and pulmonary dosing of amorphous nanoparticulate itraconazole (ITZ) compositions as well as the Sporanox oral solution (itraconazole/Janssen). Second, the steady state partitioning of ITZ in lung tissue and circulatory compartments following repeated oral and pulmonary dosing was determined. The pulmonary formulation (ITZ-pulmonary) consisted of ITZ, polysorbate 80, and poloxamer 407 in a 1:0.75:0.75 ratio and the oral formulation (ITZ-oral) consisted of ITZ, PEG 8000, poloxamer 188, and sorbitan monooleate 80 in a 1:1:2:1 ratio. Mice were dosed every 12 h by nebulization with ITZ-pulmonary, or by oral gavage with ITZ-oral or Sporanox oral solution (n = 12 per study arm). ITZ-pulmonary achieved significantly greater (>10-fold) lung tissue concentrations compared to the Sporanox oral solution and ITZ-oral. There were no statistical differences between the two oral formulations. ITZ-pulmonary achieved significantly greater lung levels per unit serum concentration compared to the orally dosed ITZ compositions. High and sustained lung tissue concentrations were achieved via inhalation of an amorphous nanoparticulate ITZ-pulmonary composition while maintaining serum levels which are above the minimum lethal concentration (MLC) of Aspergillus fumigatus.

Administration, Oral↗

Compression behaviour and tablet-forming ability of spray-dried amorphous composite particles.

The aim of this study was to investigate the compression behaviour and tablet-forming ability of spray-dried amorphous two- and three-component composite particles. Particles of lactose alone, two-component particles of lactose and PVP, and three-component particles of lactose, PVP and a small amount of polysorbate 80 were prepared by spray-drying. Two qualities of PVP with different molecular weights were used for the preparation of both types of particles. The particles were characterised with respect to permeametry surface area, moisture content, particle and bulk density, glass transition and crystallisation temperature, and heat of crystallisation. The tablet tensile strength of the different particles formed at a series of applied pressures was determined and compression parameters were derived from the Heckel and Kawakita equations. The presence of PVP gave particles that were less prone to deform permanently during compression while the presence of surfactant gave particles that were less able to form tablets. In conclusion, the compression behaviour and tablet-forming ability of spray-dried amorphous lactose can be modulated by the addition of stabilising polymers or surfactants to the spray feed solution.

Compressive Strength↗

Stabilization of solid dispersions of nimodipine and polyethylene glycol 2000.

Previous investigations revealed that solid dispersions consisting of 20% (m/m) nimodipine and 80% (m/m) polyethylene glycol 2000 prepared by the melting method, represent supersaturated solid solutions of nimodipine recrystallizing upon storage at +25 degrees C. The objective of this study was the improvement of the storage stability by preventing recrystallization. The first approach in order to prevent recrystallization was the development of thermodynamically stable solid solutions by using solvents aiming to enhance the solubility of nimodipine in the carrier material. As potential solubility enhancing additives, polyethylene glycol 300, poly(ethylene/propylene glycol) copolymer, polypropylene glycol 1020, propylene glycol, glycerol and ethyl acetate were evaluated. The second approach enhancing storage stability was the addition of recrystallization inhibitors to supersaturated solid solutions, thereby delaying the transformation of the metastable supersaturated system to the thermodynamically stable state. Macrogol cetostearyl ether, macrogol glycerol monostearate, polysorbate 60, cetostearyl alcohol, glycerol monostearate and sodium lauryl sulphate as well as hydroxypropylcellulose, butylmethacrylat-(2-dimethylaminoethyl)methacrylat-methylmethacrylat-copolymer, polyacrylic acid, polyvinyl alcohol and povidone K17 were included in the study. It could be shown that povidone K17 effectively prevents recrystallization in solid solutions containing 20% (m/m) of nimodipine during storage at +25 degrees C over silica gel thereby ensuring a substantial increase in the dissolution rate and degree of supersaturation in water. On the contrary, stabilization by solubility enhancement was only successful at drug loadings not exceeding 1% (m/m) using polyethylene glycol 300 as solubility enhancing additive.

Calcium Channel Blockers↗

Effect of combined use of nonionic surfactant on formation of oil-in-water microemulsions.

PURPOSE: This study evaluated the effects of combined use of two nonionic surfactants on the characteristics (i.e., appearance, emulsification time, and particle size) of oil-in-water microemulsions generated from flurbiprofen-loaded preconcentrates. METHODS: Three phase diagrams were constructed using Capmul PG8 (propylene glycol monocaprylate) as the oil, Tween 20 (polysorbate 20) and/or Cremophor EL (polyoxyl 35 castor oil) as surfactants. A number of preconcentrates were selected based on phase diagrams: O20T80 (20% Capmul PG8, 80% Tween 20), O20C80 (20% Capmul PG8, 80% Cremophor EL), O20T40C40 (20% Capmul PG8, 40% Tween 20, 40% Cremophor EL). Flurbiprofen loading in preconcentrates was tested at 0%, 1%, 2.5%, and 5% (w/w). The resulting mixtures of these preconcentrates upon dilution 100-fold with aqueous medium were characterized by visual and microscopic observation, HPLC and photon correlation spectroscopy. RESULTS: (a) For preconcentrates using single surfactant, either O20T80 or O20C80, the dilution generated emulsions with visible cloudiness. The particle size increased as the drug loading increased; (b) for preconcentrates using two surfactants O20T40C40, the dilution generated clear microemulsions with small particle sizes (10-11nm), and the increased drug loading seemed to have little effect on the particle size. The microemulsions from preconcentrate O20T40C40 was also found to be stable at ambient temperature over 20 days without significant change in particle size at different drug loadings. Dilution with different aqueous medium, either water, or simulated gastric fluid or simulated intestinal fluid, also did not change the particle sizes of the microemulsions. CONCLUSIONS: The combined use of surfactants in preconcentrate showed the promise in generating desired self-emulsifying microemulsions with small particle size, increased drug loading, and improved physical stability. This will have significant implications in future dosage development for poorly water-soluble drugs in using self-emulsifying microemulsions drug delivery system (SMEDDS).

Drug Combinations↗

Release behavior of diethylhexyl phthalate from the polyvinyl-chloride tubing used for intravenous administration and the plasticized PVC membrane.

The release behavior of diethylhexyl phthalate (DEHP) from polyvinyl-chloride (PVC) tubing, which composes materials in an intravenous administration set, was investigated using polysorbate 80 (Tween 80) aqueous solutions. When Tween 80 solution was circulated in PVC tubing, the amount of DEHP released increased with increasing circulation velocity and temperature. In order to clarify the effect of temperature on the release behavior of DEHP, PVC films containing varying amounts of DEHP were mounted on a cylindrical shaft and rotated at 5 and 40 degrees C. The cumulative amount of DEHP released increased with an increase in temperature, the diffusion coefficients [Dx10(-10) cm2 min-1] at 5 and 40 degrees C were 9.1 and 156.0, respectively. The glass transition temperature (Tg) of PVC films decreased with an increase in DEHP in the PVC film, as measured by differential scanning calorimeter (DSC) and release of DEHP occurred at temperatures above Tg. These results indicate that the release of DEHP from PVC tubing is closely associated with the state of the PVC and is related to diffusion of DEHP throughout the PVC.

Algorithms↗

Drug release and permeation studies of nanosuspensions based on solidified reverse micellar solutions (SRMS).

Solidified reverse micellar solutions (SRMS), i.e. mixtures of lecithin and triglycerides, offer high solubilisation capacities for different types of drugs in contrast to simple triglyceride systems [Friedrich, I., Müller-Goymann, C.C., 2003. Characterisation of SRMS and production development of SRMS-based nanosuspensions. Eur. J. Pharm. Biopharm. 56, 111-119]. Nanosuspensions based on SRMS were prepared by homogenisation close to the melting point of the SRMS matrix. In a first step the SRMS matrices of 1:1 (w/w) ratios of lecithin and triglycerides were loaded with 17beta-estradiol-hemihydrate (EST), hydrocortisone (HC) or pilocarpine base (PB), respectively, and subsequently ground in liquid nitrogen to minimise drug diffusion later on. The powder was then dispersed in a polysorbate 80 solution using high pressure homogenisation. The drug loading capacities of the nanosuspensions were very high in the case of poorly water-soluble EST (99% of total 0.1%, w/w, EST) and HC (97% of total 0.5%, w/w, HC) but not sufficient with the more hydrophilic PB (37-40% of total 1.0%, w/w, PB). These findings suggest SRMS-based nanosuspensions to be promising aqueous drug carrier systems for poorly soluble drugs like EST and HC. Furthermore, in vitro drug permeation from the different drug-loaded nanosuspensions was performed across human cornea construct (HCC) as an organotypical cell culture model. PB permeation did not differ from the nanosuspension and an aqueous solution whereas the permeation coefficients of HC-loaded nanosuspensions were reduced in comparison to aqueous and oily solutions of HC. However, the permeated amount was higher from the nanosuspensions due to a much lower HC concentration in the solution than that in the nanosuspension (solution 0.02%, w/w, versus nanosuspension 0.5%, w/w). The high drug load of the nanoparticles provides prolonged HC release. Permeated amounts of EST were reduced in comparison to HC and only detectable with an ELISA technique. The EST release from nanosuspensions and different EST-loaded systems revealed a prolonged EST release from the nanoparticulate systems in contrast to a faster release of an oily solution of an equal EST concentration. With regard to an aqueous EST suspension of similar concentration which represents a depot system the release rate from the nanosuspensions revealed the same order of magnitude which points again to a prolonged release potential of the nanosuspensions.

Cell Line↗