-
The Journal of Pharmacy and Pharmacology Aug 2013Over the past few decades, mathematical modelling and simulation of drug delivery systems has been steadily gained interest as a focus for academic and industrial...
OBJECTIVES
Over the past few decades, mathematical modelling and simulation of drug delivery systems has been steadily gained interest as a focus for academic and industrial attention. Here, simulation of dexamethasone (DEX, a corticosteroid anti-inflammatory agent) release profile from drug-eluting cochlear implant coatings is reported using artificial neural networks.
METHODS
The devices were fabricated as monolithic dispersions of the pharmaceutically active ingredient in a silicone rubber matrix. A two-phase exponential model was fitted on the experimentally obtained DEX release profiles. An artificial neural network (ANN) was trained to determine formulation parameters (i.e. DEX loading percentage, the devices surface area and their geometry) for a specific experimentally obtained drug release profile. In a reverse strategy, an ANN was trained for determining expected drug release profiles for the same set of formulation parameters.
KEY FINDINGS
An algorithm was developed by combining the two previously developed ANNs in a serial manner, and this was successfully used for simulating the developed drug-eluting cochlear implant coatings. The models were validated by a leave-one-out method and performing new experiments.
CONCLUSIONS
The developed ANN algorithms were capable to bilaterally predict drug release profile for a known set of formulation parameters or find out the levels for input formulation parameters to obtain a desired DEX release profile.
Topics: Chemistry, Pharmaceutical; Cochlear Implants; Computer Simulation; Delayed-Action Preparations; Dexamethasone; Drug Delivery Systems; Equipment Design; Neural Networks, Computer; Silicone Elastomers; Solubility
PubMed: 23837582
DOI: 10.1111/jphp.12086 -
Annals of Clinical Biochemistry Nov 2019
Topics: Blood Chemical Analysis; Dexamethasone; Finger Joint; Humans; Joint Diseases; Limit of Detection; Retrospective Studies
PubMed: 31370673
DOI: 10.1177/0004563219870834 -
Steroids 1988A sensitive radioimmunoassay for dexamethasone 17,21-dipropionate and its four metabolites in human plasma and urine has been developed using single anti-dexamethasone...
A sensitive radioimmunoassay for dexamethasone 17,21-dipropionate and its four metabolites in human plasma and urine has been developed using single anti-dexamethasone antiserum. The antiserum was obtained by immunizing rabbits with dexamethasone-3-oxime-bovine serum albumin conjugate. All of the endogenous steroids tested cross-reacted less than 0.07%. Before radioimmunoassay, dexamethasone 17,21-dipropionate and dexamethasone 17-propionate were hydrolyzed to dexamethasone, and 6 beta-OH-dexamethasone 17-propionate was hydrolyzed to 6 beta-OH-dexamethasone in 3% ammonia/methanol at 5 C for 16 h. A standard curve was established with a useful range between 0.005 and 2 ng in the case of dexamethasone, between 0.05 and 5 ng in the case of 6 beta-OH-dexamethasone. Measurement of plasma concentrations and percent urinary excretion of the metabolites in healthy men was performed following occlusive dressing of dexamethasone 17,21-dipropionate cream and ointment. The main metabolites in plasma were dexamethasone 17-propionate and dexamethasone, which increased gradually and reached maximum levels (160-200 pg/mL) at 24-32 h after application. The major metabolites observed in urine were 6 beta-OH-dexamethasone 17-propionate and 6 beta-OH-dexamethasone. Total percentage of their urinary excretions within 72 h after application amounted to 0.28-0.50% of the dose administered.
Topics: Administration, Topical; Adult; Animals; Chromatography, High Pressure Liquid; Dexamethasone; Humans; Hydrolysis; Male; Rabbits; Radioimmunoassay; Reproducibility of Results
PubMed: 3247667
DOI: 10.1016/0039-128x(88)90222-x -
Therapeutic Drug Monitoring Oct 1999Pharmacokinetics of intravenous and oral pulsed high-dose dexamethasone were studied in four patients with pemphigus vulgaris. Doses for dexamethasone were varied from... (Comparative Study)
Comparative Study
Pharmacokinetics of intravenous and oral pulsed high-dose dexamethasone were studied in four patients with pemphigus vulgaris. Doses for dexamethasone were varied from 100 to 300 mg. Serum concentrations were measured by high-performance liquid chromatographic procedure with diode assay detection. Bioavailability was assessed by comparing the areas under the serum concentration-time curves following oral administration with those of intravenous administration. Mean bioavailability of high-dose oral dexamethasone was 63.4%. Side effects were minor and were limited to temporary facial flushing both after oral and intravenous administration. Oral administration of dexamethasone in pemphigus patients showed to be more convenient and cost effective than administration by the intravenous route.
Topics: Administration, Oral; Adult; Biological Availability; Chromatography, High Pressure Liquid; Dexamethasone; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Pemphigus; Time Factors
PubMed: 10519450
DOI: 10.1097/00007691-199910000-00007 -
European Journal of Pharmaceutics and... Aug 2009Compared with traditional drug solutions or suspensions, polymeric microparticles represent a valuable means to achieve controlled and prolonged drug delivery into... (Comparative Study)
Comparative Study
Dexamethasone-containing biodegradable superparamagnetic microparticles for intra-articular administration: physicochemical and magnetic properties, in vitro and in vivo drug release.
Compared with traditional drug solutions or suspensions, polymeric microparticles represent a valuable means to achieve controlled and prolonged drug delivery into joints, but still suffer from the drawback of limited retention duration in the articular cavity. In this study, our aim was to prepare and characterize magnetic biodegradable microparticles containing dexamethasone acetate (DXM) for intra-articular administration. The superparamagnetic properties, which result from the encapsulation of superparamagnetic iron oxide nanoparticles (SPIONs), allow for microparticle retention with an external magnetic field, thus possibly reducing their clearance from the joint. Two molecular weights of poly(lactic-co-glycolic acid) (PLGA) were used, 12 and 19 kDa. The prepared batches were similar in size (around 10 microm), inner morphology, surface morphology, charge (neutral) and superparamagnetic behaviour. The SPION distribution in the microparticles assessed by TEM indicates a homogeneous distribution and the absence of aggregation, an important factor for preserving superparamagnetic properties. DXM release profiles were shown to be quite similar in vitro (ca. 6 days) and in vivo, using a mouse dorsal air pouch model (ca. 5 days).
Topics: Absorbable Implants; Animals; Calorimetry, Differential Scanning; Crystallization; Crystallography; Dexamethasone; Ferric Compounds; Injections, Intra-Articular; Magnetics; Mice; Mice, Inbred C57BL; Microspheres; X-Ray Diffraction
PubMed: 19303928
DOI: 10.1016/j.ejpb.2009.03.003 -
Der Internist May 1998
Topics: Anti-Inflammatory Agents; Brain Edema; Cerebral Hemorrhage; Dexamethasone; Humans; Treatment Outcome
PubMed: 9647995
DOI: No ID Found -
Journal of Pharmacy Practice Apr 2021
Topics: Dexamethasone; Humans; COVID-19 Drug Treatment
PubMed: 33302762
DOI: 10.1177/0897190020979608 -
Journal of Controlled Release :... Feb 2014Aseptic implant loosening related to implant wear particle-induced inflammation is the most common cause of failure after joint replacement. Modulation of the...
Aseptic implant loosening related to implant wear particle-induced inflammation is the most common cause of failure after joint replacement. Modulation of the inflammatory reaction to the wear products represents a rational approach for preventing aseptic implant failure. Long-term treatment using anti-inflammatory agents, however, can be associated with significant systemic side effects due to the drugs' lack of tissue specificity. To address this issue, N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-dexamethasone conjugate (P-Dex) was developed and evaluated for prevention of wear particle-induced osteolysis and the loss of fixation in a murine prosthesis failure model. Daily administration of free dexamethasone (Dex) was able to prevent wear particle-induced osteolysis, as assessed by micro-CT and histological analysis. Remarkably, monthly P-Dex administration (dose equivalent to free Dex treatment) was equally effective as free dexamethasone, but was not associated with systemic bone loss (a major adverse side effect of glucocorticoids). The reduced systemic toxicity of P-Dex is related to preferential targeting of the sites of wear particle-induced inflammation and its subcellular sequestration and retention by local inflammatory cell populations, resulting in sustained therapeutic action. These results demonstrate the feasibility of utilizing a macromolecular prodrug with reduced systemic toxicity to prevent wear particle-induced osteolysis.
Topics: Acrylamides; Animals; Delayed-Action Preparations; Dexamethasone; Humans; Male; Mice; Osteolysis; Prodrugs; Prosthesis Failure
PubMed: 24326124
DOI: 10.1016/j.jconrel.2013.11.024 -
American Journal of Veterinary Research Jan 2002To determine whether iontophoretic administration of dexamethasone to horses results in detectable concentrations in synovial fluid, plasma, and urine. (Clinical Trial)
Clinical Trial Randomized Controlled Trial
OBJECTIVE
To determine whether iontophoretic administration of dexamethasone to horses results in detectable concentrations in synovial fluid, plasma, and urine.
ANIMALS
6 adult mares.
PROCEDURE
Iontophoresis was used to administer dexamethasone. Treatments (4 mA for 20 minutes) were administered to a tarsocrural joint of each mare. The drug electrode contained 3 ml of dexamethasone sodium phosphate at a concentration of 4 or 10 mg/ml. Samples of synovial fluid, blood, and urine were obtained before and 0.5, 4, 8, and 24 hours after each treatment. All samples were tested for dexamethasone using an ELISA. Synovial fluid also was evaluated for dexamethasone, using high-performance liquid chromatography.
RESULTS
The lower and upper limits of detection for dexamethasone in synovial fluid with the ELISA were 0.21 and 1.5 ng/ml, respectively. Dexamethasone administered at a concentration of 10 mg/ml was detected by the ELISA in synovial fluid of 5 mares from 0.5 to 24 hours and in urine of 4 mares from 0.5 to 8 hours after each treatment, but it was not detected in plasma. Mean synovial fluid concentration of dexamethasone was 1.01 ng/ml. Dexamethasone administered at a concentration of 4 mg/ml was detected by the ELISA in urine of 2 mares at 0.5 and 4 hours after treatment, but it was not detected in synovial fluid or plasma.
CONCLUSIONS AND CLINICAL RELEVANCE
Iontophoresis cannot be considered an effective method for delivery of dexamethasone to synovial fluid of horses, because drug concentrations achieved in this study were less than therapeutic concentrations.
Topics: Animals; Dexamethasone; Dose-Response Relationship, Drug; Female; Hindlimb; Horses; Iontophoresis; Joints; Synovial Fluid
PubMed: 16206773
DOI: 10.2460/ajvr.2002.63.11 -
Otology & Neurotology : Official... Aug 2011To measure dexamethasone concentrations in the plasma and perilymph of the human ear after intravenous (IV) and intratympanic (IT) administration and to compare these... (Comparative Study)
Comparative Study
OBJECTIVE
To measure dexamethasone concentrations in the plasma and perilymph of the human ear after intravenous (IV) and intratympanic (IT) administration and to compare these with previous studies with methylprednisolone.
METHODS
Patients were administered dexamethasone by the IT or IV routes approximately 0.5 to 2 hours before cochlear implantation. The IT dose of 1.6 to 7.2 mg (0.4-1.8 ml of a 4 mg/ml solution) of dexamethasone sodium phosphate was administered by injection into the middle ear cavity through the external auditory canal via a 27-gauge needle passed through a small anterosuperior myringotomy. The IV dose of dexamethasone sodium phosphate was 0.17 mg/kg given as a single injection for 30 seconds. A sample of perilymph (approximately 20 μl) was collected using a needle passed through the round window, and blood was sampled simultaneously. Concentrations of free dexamethasone and dexamethasone sodium phosphate were measured using a validated liquid chromatography-tandem mass spectrometry method.
RESULTS
In the 22 patients studied, 22 perilymph samples and 19 plasma samples were available and suitable for measurement. The median perilymph concentration of dexamethasone after IV injection of 0.17 mg/kg was 0.016 mg/L (n = 9; range, 0.008-0.17), and 1.4 mg/L (n = 13; range, 0.1-16.3) after IT administration of approximately 4 mg. Perilymph concentrations were approximately 88-fold higher after IT compared with IV administration (p = 0.0004) or approximately 260 fold after correction for dosage. The median plasma concentration of dexamethasone after IV injection was 0.12 mg/L (n = 7; range, 0.07-0.14) and 0.003 mg/L (n = 12; range, <0.0005-0.005) after IT injection. Plasma concentrations were approximately 40-fold lower (p = 0.0005) or approximately 13-fold lower after dose correction. Concentrations of dexamethasone sodium phosphate were more variable and were even higher in perilymph and lower in plasma.
CONCLUSION
Administration of dexamethasone IT results in much higher perilymph concentrations and much lower plasma concentrations compared with IV administration.
Topics: Adolescent; Adult; Aged; Dexamethasone; Ear, Middle; Female; Humans; Injections; Injections, Intravenous; Male; Middle Aged; Perilymph; Tympanic Membrane
PubMed: 21725263
DOI: 10.1097/MAO.0b013e3182255933