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1.
Article in English | MEDLINE | ID: mdl-35867536

ABSTRACT

A monoclonal antibody against triamcinolone acetonide (TCA) and budesonide (BUD) was prepared using a hapten that was generated by introducing a carboxyl group into the structure of TCA. Based on the prepared monoclonal antibody, a gold nanoparticle-based lateral-flow immunoassay (GLFA) was developed with the ability to screen TCA and BUD in milk. The visible limits of detection of the GLFA for the analysis of TCA and BUD were 0.1 and 0.5 ng/mL with a cutoff value of 5 and 10 ng/mL, respectively, in milk. Average recoveries of TCA and BUD in milk were 92.0-102.2% and 96.0-98.8% with a good correlation between the results from the GLFA and LC-MS/MS analysis. These results demonstrated that the GLFA method for the rapid detection of TCA and BUD in milk samples is reliable and sensitive.


Subject(s)
Metal Nanoparticles , Milk , Allergens/analysis , Animals , Antibodies, Monoclonal , Budesonide/analysis , Chromatography, Liquid , Gold , Gold Colloid/chemistry , Immunoassay/methods , Limit of Detection , Milk/chemistry , Tandem Mass Spectrometry , Triamcinolone Acetonide/analysis
2.
Biomed Chromatogr ; 36(2): e5264, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34653273

ABSTRACT

Triamcinolone acetonide (TAA) is the drug of choice in the management of ocular inflammations due to its anti-inflammatory and immuno-suppressant activity. Available marketed formulations (Triesence, Trivaris, Kenalog) are in the suspension form recommended to be administered via intravitreal injection, which has many major complications. In the present study, we have designed and evaluated Hydroxypropyl-ß-cyclodextrin (HP-ß-CD),) based conventional formulations of TAA (aqueous suspensions) with different dose strengths to identify the dose strength required for achieving the effective concentrations in vitreous humor following pre-corneal administration of the formulations. Ocular pharmacokinetic studies of conventional formulations of triamcinolone acetonide (TAA) with different dose strengths (1 mg/30µL, 2 mg/30µL, 4 mg/30µL) were performed to identify the dose strength required to produce effective concentrations of TAA in the aqueous and vitreous humor. A rapid, sensitive, selective, accurate and precise bioanalytical method utilizing a small sampling volume (<45 µL) was developed and validated for quantification of TAA in the samples obtained from the ocular pharmacokinetic studies. Aqueous suspensions of TAA with 20% HP-ß-CD produced time course profiles in the aqueous humor at all the dose strengths. However, measurable concentrations and time course of TAA in vitreous humor were achieved only with 4 mg/30µL dose strength.


Subject(s)
Chromatography, High Pressure Liquid/methods , Cornea/metabolism , Triamcinolone Acetonide , Vitreous Body/chemistry , 2-Hydroxypropyl-beta-cyclodextrin/chemistry , Animals , Limit of Detection , Linear Models , Male , Rabbits , Reproducibility of Results , Triamcinolone Acetonide/analysis , Triamcinolone Acetonide/metabolism , Triamcinolone Acetonide/pharmacokinetics , Uveitis, Posterior
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 214: 302-308, 2019 May 05.
Article in English | MEDLINE | ID: mdl-30798211

ABSTRACT

Triamcinolone acetonide (TCA) abuse in cosmetics is a common phenomenon. A rapid lateral flow immunochromatographic assay (ICA) was developed for the quantitative detection of TCA using a probe based on upconversion luminescence nanoparticles. Lanthanide-doped upconversion nanoparticles (UCNPs) were synthesized in a system comprising water and ethylene glycol, and a silicon dioxide layer was covered at the carboxyl site. A binding site protection strategy was used to decrease the background signal of UCNPs-ICA. Using dexamethasone derivative as a coating antigen, the optimal UCNPs-ICA exhibits good dynamic linear detection for TCA in the range 1.0-100 ng mL-1 with a median inhibitory concentration of 9.8 ng mL-1. The detection limits for TCA in a cosmetic sample are 20 µg kg-1. The pretreatment of samples only needs dilution with water, suggesting the assay can quantitate TCA on-site using a portable upconversion luminescence reader with a cumulative analysis time of only 10 min.


Subject(s)
Cosmetics/analysis , Luminescent Measurements/methods , Nanoparticles/chemistry , Triamcinolone Acetonide/analysis , Animals , Antibodies, Monoclonal, Murine-Derived/chemistry , Ethylene Glycol/chemistry , Humans , Immunoassay/methods , Mice , Silicon Dioxide/chemistry , Triterpenes/chemistry
4.
J AOAC Int ; 101(4): 981-991, 2018 Jul 01.
Article in English | MEDLINE | ID: mdl-28903833

ABSTRACT

Two specific, sensitive, and precise stability-indicating chromatographic methods have been developed for the determination of triamcinolone acetonide (TMC) and its coformulated drug, econazole nitrate (ECZ), in the presence of TMC impurities and degradation products. The first method was based on HPTLC-spectrodensitometry in which resolution and quantitation was achieved by using silica gel 60 F254 HPTLC plates and an ethyl acetate-tetrahydrofuran-ammonia mobile phase (10.0 + 7.0 + 0.1, v/v/v). The second method was a reversed-phase HPLC method in which separation was achieved using an acetonitrile-methanol-0.05 M potassium dihydrogen phosphate mobile phase, pH 3.0 (25.0 + 15.0 + 60.0, v/v/v). In both methods, the separated components were detected at 225 nm. Validation of both methods was conducted in compliance with International Conference on Harmonization (ICH) guidelines, and system suitability was confirmed. The linearity ranges were 0.20-28.00 and 0.50-55.00 µg/band for TMC and ECZ by HPTLC, whereas for HPLC, the range was 0.05-30.00 and 1.00-40.00 µg/mL for both drugs, respectively. The methods were successfully applied for the analysis of a pharmaceutical formulation and were compared with the reported method with no significant difference.


Subject(s)
Chromatography, High Pressure Liquid/methods , Chromatography, Thin Layer/methods , Triamcinolone Acetonide/analysis , Chromatography, Reverse-Phase/methods , Drug Combinations , Drug Contamination , Drug Stability , Econazole/analysis , Reproducibility of Results , Sensitivity and Specificity , Triamcinolone Acetonide/chemistry
5.
J Sep Sci ; 39(14): 2689-701, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27184267

ABSTRACT

An ultra high performance liquid chromatography method was developed and validated for the quantitation of triamcinolone acetonide in an injectable ophthalmic hydrogel to determine the contribution of analytical method error in the content uniformity measurement. During the development phase, the design of experiments/design space strategy was used. For this, the free R-program was used as a commercial software alternative, a fast efficient tool for data analysis. The process capability index was used to find the permitted level of variation for each factor and to define the design space. All these aspects were analyzed and discussed under different experimental conditions by the Monte Carlo simulation method. Second, a pre-study validation procedure was performed in accordance with the International Conference on Harmonization guidelines. The validated method was applied for the determination of uniformity of dosage units and the reasons for variability (inhomogeneity and the analytical method error) were analyzed based on the overall uncertainty.


Subject(s)
Hydrogels/chemistry , Triamcinolone Acetonide/analysis , Chromatography, High Pressure Liquid , Monte Carlo Method
6.
Anal Chem ; 88(24): 12051-12059, 2016 12 20.
Article in English | MEDLINE | ID: mdl-28193015

ABSTRACT

Osteoarthritis (OA), characterized by degeneration of the cartilaginous tissue in articular joints, severely impairs mobility in many people worldwide. The degeneration is thought to be mediated by inflammatory processes occurring in the tissue of the joint, including the cartilage. Intra-articular administered triamcinolone acetonide (TAA) is one of the drug treatments employed to ameliorate the inflammation and pain that characterizes OA. However, the penetration and distribution of TAA into the avascular cartilage is not well understood. We employed matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which has been previously used to directly monitor the distribution of drugs in biological tissues, to evaluate the distribution of TAA in human cartilage after in vitro incubation. Unfortunately, TAA is not easily ionized by regular electrospray ionization (ESI) or MALDI. To overcome this problem, we developed an on-tissue derivatization method with Girard's reagent T (GirT) in human incubated cartilage being able to study its distribution and quantify the drug abundance (up to 3.3 ng/µL). Our results demonstrate the depth of penetration of a corticosteroid drug in human OA cartilage using MALDI-MSI.


Subject(s)
Anti-Inflammatory Agents/analysis , Cartilage/chemistry , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Triamcinolone Acetonide/analysis , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/therapeutic use , Betaine/analogs & derivatives , Betaine/chemistry , Cartilage/metabolism , Cartilage/pathology , Humans , Osteoarthritis/drug therapy , Osteoarthritis/metabolism , Osteoarthritis/pathology , Triamcinolone Acetonide/chemistry , Triamcinolone Acetonide/therapeutic use
7.
Int Endod J ; 44(12): 1162-9, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21902701

ABSTRACT

AIM: To investigate the chemical interaction of calcium hydroxide with the corticosteroid triamcinolone acetonide in Ledermix Paste and in Odontopaste, a new steroid/antibiotic paste. METHODOLOGY: Validated methods were developed to analyse the interaction of calcium hydroxide in two forms, Pulpdent Paste and calcium hydroxide powder, with triamcinolone acetonide within Odontopaste and Ledermix Paste. High-performance liquid chromatography (HPLC) was used to analyse the mixed samples of the pastes and calcium hydroxide. The concentration of triamcinolone acetonide within the pastes was determined over 0, 2, 6, 24 and 72-h time-points. All tests with the HPLC involved the testing of the standard with triplicate injections alongside the samples. All samples were tested in duplicate with each injected twice; therefore, four tests were performed for each investigation. Linearity, precision and specificity of the testing procedures and apparatus were validated. Descriptive statistics are provided. RESULTS: In both pastes, there was a marked rapid destruction of the triamcinolone acetonide steroid upon mixing with calcium hydroxide. Odontopaste suffered a lower rate of destruction of the triamcinolone acetonide component than Ledermix Paste, but both pastes showed very similar degrees of steroid destruction after 72 h. When using calcium hydroxide powder with Ledermix Paste, the triamcinolone was destroyed entirely and immediately. CONCLUSION: The addition of calcium hydroxide to Odontopaste or Ledermix Paste results in the rapid destruction of the steroid.


Subject(s)
Anti-Bacterial Agents/chemistry , Calcium Hydroxide/chemistry , Clindamycin/chemistry , Demeclocycline/chemistry , Root Canal Irrigants/chemistry , Triamcinolone Acetonide/chemistry , Alkalies/chemistry , Anti-Bacterial Agents/analysis , Calcium Hydroxide/analysis , Chromatography, High Pressure Liquid , Clindamycin/analysis , Demeclocycline/analysis , Drug Combinations , Drug Interactions , Humans , Hydrogen-Ion Concentration , Materials Testing , Powders , Root Canal Irrigants/analysis , Time Factors , Triamcinolone Acetonide/analysis
8.
J Chromatogr B Analyt Technol Biomed Life Sci ; 879(7-8): 548-52, 2011 Mar 01.
Article in English | MEDLINE | ID: mdl-21296037

ABSTRACT

A sensitive and selective liquid chromatographic-tandem mass spectrometric method was developed for quantification of triamcinolone acetonide (TA) in rabbit ocular tissues. After a simple liquid-liquid extraction using tert-butyl methyl ether, TA and internal standard methylprednisolone were separated on a C18 column with a mobile phase of acetonitrile:water:formic acid (60:40:0.1, v/v/v) and quantified by the use of selected reaction monitoring mode with a total run time of 4 min. The method was validated in tissue homogenates with a daily working range of 1-1000 ng/mL with correlation coefficient of more than 0.99 and a sensitivity of 1 ng/mL as lower limit of quantification, respectively. The mean intra-day and inter-day precisions were less than 10% and accuracy values were higher than 90%. This method was fully validated for the accuracy, precision and stability studies. The method proved to be accurate and specific, and was applied to an in vivo biodistribution study of TA after intravitreal injection to rabbits. Values of mean residence time in vitreous humor, crystalline lens and aqueous humor were 27.7, 35.8 and 20.0 days, respectively.


Subject(s)
Aqueous Humor/chemistry , Chromatography, Liquid/methods , Lens, Crystalline/chemistry , Tandem Mass Spectrometry/methods , Triamcinolone Acetonide/analysis , Vitreous Body/chemistry , Animals , Aqueous Humor/metabolism , Drug Stability , Intravitreal Injections , Lens, Crystalline/metabolism , Male , Rabbits , Reproducibility of Results , Sensitivity and Specificity , Tissue Distribution , Triamcinolone Acetonide/administration & dosage , Triamcinolone Acetonide/pharmacokinetics , Vitreous Body/metabolism
9.
Can J Ophthalmol ; 45(6): 621-6, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20935694

ABSTRACT

OBJECTIVE: To assess the efficacy of surgical excision of sub-Tenon triamcinolone acetonide (TA) deposits in the control of steroid-induced glaucoma. DESIGN: Prospective, nonrandomized, interventional case series. PARTICIPANTS: Eighteen eyes of 14 subjects with increased IOP within 6 months of sub-Tenon TA injection who did not respond to medical antiglaucomatous treatment were included in the study. METHODS: Under topical anaesthesia, steroid deposits were completely excised and placed in ethyl alcohol for the determination of the TA amount using high-performance liquid chromatography. The patients were followed up for 6 months and a paired-sample t test was used to compare mean IOP before and after excision of sub-Tenon TA deposits. RESULTS: The mean IOP levels before and after the sub-Tenon steroid injections were 15.9 (SD 2.9) mm Hg and 36.4 (SD 8.4) mm Hg, respectively (p < 0.001). IOP levels decreased significantly after the removal of the deposits (mean 15.3 [SD 2.1] mm Hg) (p < 0.001). Within 6 months of follow-up, all glaucoma medications were stopped in 9 subjects without further IOP increase, whereas IOP control in 5 subjects necessitated using glaucoma medications. The median TA amount was found to be 7.35 mg (range 3.3-29.68 mg). IOP decrease after the excision showed no correlation with the amount of TA (p = 0.8). CONCLUSIONS: Surgical excision of the sub-Tenon steroid deposit should be considered as the primary treatment for steroid-induced glaucoma refractory to medical treatment.


Subject(s)
Glaucoma, Open-Angle/chemically induced , Glaucoma, Open-Angle/surgery , Glucocorticoids/adverse effects , Intraocular Pressure/drug effects , Tenon Capsule/surgery , Triamcinolone Acetonide/adverse effects , Adult , Aged , Aged, 80 and over , Chromatography, High Pressure Liquid , Eye Diseases/drug therapy , Female , Glucocorticoids/analysis , Humans , Male , Middle Aged , Ophthalmologic Surgical Procedures , Prospective Studies , Tenon Capsule/drug effects , Tonometry, Ocular , Triamcinolone Acetonide/analysis
10.
J Gene Med ; 12(8): 669-80, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20635325

ABSTRACT

BACKGROUND: Nuclear membrane is one of the main barriers in polymer mediated intracellular gene delivery. To improve the transgenic activity and safety of nonviral vector, triamcinolone acetonide (TA) as a nuclear localization signal was conjugated with different molecular weight polyethylenimine (PEI). METHODS: Different molecular weight PEI [600, 1800, 25,000 (25k)] was conjugated with TA to synthesize PEI-TA by two-step reaction. Their physicochemical characteristics, in vitro cytotoxicity and transfection efficiency were evaluated. To investigate the difference of transfection efficiency of various molecular weight PEI-TA, their transfection mechanism was further investigated by confocal microscopy and competition assay. Transgenic expression in vivo was evaluated by injection into hepatic portal vein of mice. RESULTS: All PEI-TA could form nanosize polyplexes with DNA and their physicochemical properties resemble each other. Their cytotoxicities were negligible compared to PEI 25k. The order of transfection efficiency was PEI 1800-TA > PEI 600-TA > PEI 25k-TA. A transfection mechanism study displayed that TA could inhibit considerably the transgenic activity of PEI 1800-TA and PEI 600-TA, but that of PEI 25k-TA was not inhibited. It was suggested that PEI 1800-TA and PEI 600-TA might translocate into the nucleus. Confocal microscopy investigation verified this suggestion. The data strongly suggested that the transfection efficiency of PEI 1800-TA in vivo was much higher than that of PEI 25k, which was consistent with the results obtained in vitro. CONCLUSIONS: Low molecular weight PEI-TA could translocate into the nucleus efficiently. PEI 1800-TA presented higher transgenic activity and it has a great potential for gene therapy as a nonviral carrier.


Subject(s)
Cell Nucleus/metabolism , Gene Transfer Techniques , Polyethyleneimine/chemistry , Triamcinolone Acetonide/chemistry , Animals , Genetic Therapy , Genetic Vectors , Mice , Mice, Inbred ICR , Microscopy, Electron, Transmission , Polyethyleneimine/analysis , Polyethyleneimine/toxicity , Transfection , Triamcinolone Acetonide/analysis , Triamcinolone Acetonide/toxicity
11.
Talanta ; 76(3): 597-601, 2008 Jul 30.
Article in English | MEDLINE | ID: mdl-18585326

ABSTRACT

A pentafluorophenylpropyl (PFPP) stationary phase was for the first time tested for the simultaneous determination of triamcinolone acetonide, its degradation product triamcinolone and two preservatives, methylparaben, and propylparaben. A new simple isocratic reversed phase HPLC method with UV detection, using estradiol hemihydrate as an internal standard, has been developed and validated. Chromatography was performed on a Discovery HS F5 column (150 mm x 4.6 mm, 5 microm) using a binary mobile phase composed of acetonitrile and water 45:55 (v:v). The flow-rate was 0.6 mL/min, the column temperature 25 degrees C and the UV detection was accomplished at 240 nm. The chromatography results using PFPP stationary phase were compared with those obtained using conventional C18 columns.


Subject(s)
Chromatography, High Pressure Liquid/methods , Triamcinolone Acetonide/analysis , Acetonitriles , Buffers , Chromatography, High Pressure Liquid/standards , Indicators and Reagents , Water
12.
Anal Bioanal Chem ; 391(7): 2683-91, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18506427

ABSTRACT

An HPLC-DAD method for determining corticoids in calf feed and in animal feeding water samples using a monolithic column has been developed and validated. The method optimization included the study of binary mobile phases of water and acetonitrile. The optimum separation was achieved at 40 degrees C, with acetonitrile:H(2)O 29:71 v/v used as mobile phase and a 3 ml/min flow-rate, which resulted in their separation in about 5 min. Two reported sample procedures were applied to feed and for animal feeding water samples prior to HPLC. Method validation was carried out according to the EU criteria established for quantitative screening methods. The results indicate that this method is highly specific, reproducible and accurate. The proposed method was found to be robust and unaffected by small variations in the extraction procedure and in HPLC conditions. The developed method for the determination of corticoids in feed and water samples was also found to be suitable for different kinds of feeds and waters.


Subject(s)
Adrenal Cortex Hormones/analysis , Animal Feed/analysis , Chromatography, High Pressure Liquid/methods , Animals , Betamethasone/analysis , Calibration , Cattle , Cortisone/analogs & derivatives , Cortisone/analysis , Flumethasone/analysis , Fresh Water/analysis , Prednisone , Reproducibility of Results , Triamcinolone Acetonide/analysis
13.
Graefes Arch Clin Exp Ophthalmol ; 245(5): 689-96, 2007 May.
Article in English | MEDLINE | ID: mdl-17006679

ABSTRACT

BACKGROUND: To systematically investigate the common purification techniques for commercially available triamcinolone acetonide preparations and the influence of different filter parameters on final yield, reproducibility and particle size spectrum. METHODS: Two non-filter techniques using either sedimentation or centrifugation, and two different filter techniques were tested. Filters with different characteristics were investigated with the pore size ranging from 0.1 to 5.0 microm, and the filter diameter ranging from 4 to 30 mm. Only sterile standard syringe filters with low adsorptive characteristics (hydrophilic cellulose filter membranes) for pharmaceutical use were employed. For quantification, triamcinolone acetonide was dissolved in 60% methanol and measured spectrophotometrically at 239 nm. The crystal size spectrum was determined using a particle size analyzer that combines electronic pulse area analysis and resistance measurement. RESULTS: Depending on the purification technique used the resulting triamcinolone doses differed significantly. While the centrifugation method achieved purification without relevant loss, the sedimentation method yielded only 28.7% compared to the original commercial suspension, and in addition, the predictability was low (range 8.1-17.2 mg). With filter techniques high and consistent doses with a good reproducibility were achieved, but results were highly dependent on the filter characteristics. The final triamcinolone amount inversely correlated with the filter diameter due to a uniform loss of crystalline particles. In contrast, enlarging the pore size caused a substantial shift in the particle size spectrum due to a selective loss of small crystalline particles. CONCLUSIONS: The most common purification techniques vary notably in regard to final triamcinolone doses, reproducibility and particle size spectrum. The appropriate choice of the filter parameters seems to be more important than assumed, as pore size and filter diameter substantially influence both the final TA doses and the particle size of the TA crystals.


Subject(s)
Glucocorticoids/isolation & purification , Triamcinolone Acetonide/isolation & purification , Centrifugation/methods , Crystallization , Filtration/methods , Glucocorticoids/analysis , Glucocorticoids/chemistry , Particle Size , Pharmaceutical Preparations/analysis , Pharmaceutical Preparations/chemistry , Pharmaceutical Preparations/isolation & purification , Reproducibility of Results , Suspensions , Triamcinolone Acetonide/analysis , Triamcinolone Acetonide/chemistry
14.
J Chromatogr B Analyt Technol Biomed Life Sci ; 847(2): 199-204, 2007 Mar 01.
Article in English | MEDLINE | ID: mdl-17097356

ABSTRACT

Intravitreal triamcinolone acetonide (IVTA) injection has been used in the treatment of various posterior segment diseases. One of the side effects of IVTA is raised intraocular pressure, which may be secondary to triamcinolone acetonide (TAA)'s effects on the trabecular meshwork that affects aqueous outflow. In order to study the biological effects of TAA on the trabecular meshwork, we firstly need to reliably and accurately detect the concentration of TAA in tissue cells or fluids. In this study we have described a technique of using gas chromatography-electron-capture-negative-ion mass spectrometry (GC-NCI-MS) to develop a simple, sensitive, selective and validated method to detect TAA in aqueous humor (AH) of rabbits following IVTA and subconjunctival TAA injections. We derivatized TAA from extracted aqueous sample by acetic anhydride and BSTFA, respectively, and analyzed by GC-NCI-MS. The detection limit was 0.3ng/ml, linearity over 0.995 from 0 to 300ng/ml. The reproducibility ranged from 10.4 to 3.9 for concentrations from 3 to 300ng/ml, and recovery was over 95% for the concentrations 10, 60, and 200ng/ml. No interference was found from 159 aqueous samples. There was no TAA residue carried to the next injection from previously high concentration injection, 10,000ng/ml. We have provided an alternative, rapid, and robust method other than LC-MS-MS for TAA detection in AH.


Subject(s)
Aqueous Humor/metabolism , Gas Chromatography-Mass Spectrometry/methods , Triamcinolone Acetonide/analysis , Animals , Aqueous Humor/chemistry , Molecular Structure , Rabbits , Reproducibility of Results , Triamcinolone Acetonide/chemistry
15.
Ars pharm ; 48(1): 19-29, 2007. ilus, tab
Article in Es | IBECS | ID: ibc-054056

ABSTRACT

El acetónido de triamcinolona, antiinfl amatorio esteroideo, presenta por vía tópica los inconvenientes de la corticoterapia. No obstante, su incorporación a un sistema transportador, como los liposomas permitiría prolongar la dosis efectiva en el lugar de acción (dermis y epidermis), reduciendo los efectos secundarios. Así pues, se ha normalizado el método de elaboración de liposomas multilaminares portadores de acetónido de triamcinolona y evaluado el grado de captación del fármaco seleccionado, en función de la composición de los liposomas, determinando los componentes más idóneos para su obtención y los rendimientos proporcionados al variar las concentraciones de los mismos. La adición de colesterol para mejorar su estabilidad, provoca una reducción media en la captación; no obstante la encapsulación sigue siendo bastante elevada. La evaluación de la estabilidad muestra la infl uencia de la temperatura de conservación, de tal manera que los liposomas mantenidos a temperatura de refrigeración (4-6ºC) poseen una estabilidad mayor que las muestras a temperatura ambiente


In topical presentation, Triamcinolone acetonide, a steroidal anti-infl ammatory preparation, presents all the disadvantages of corticotherapy. However, on incorporation into a liposomal drug delivery system, the effectiveness of each dosage within the area of its activity (dermis and epidermis) is prolonged, serving to reduce secondary side effects. For this reason, an attempt has been made to standardize a method for the preparation of a multilaminar liposomal delivery system of triamcinolone acetonide and to assess how much of the drug could be encapsulated by the varying liposomal formulations tested and consequently, which of these would prove to be the most suitable. The addition of cholesterol to such formulations was found to improve stability. However, although such an addition was found to reduce levels of encapsulation of the drug, these still remained suffi ciently high. In the assessment of stability, storage temperature was found to bear an infl uence. Liposomes kept under cold storage (4-6ºC) presented higher stability than samples stored at room temperature


Subject(s)
Humans , Liposomes/chemistry , Triamcinolone Acetonide/analysis , Triamcinolone Acetonide/chemistry , Drug Stability , Drug Compounding
16.
Exp Eye Res ; 82(3): 479-87, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16168412

ABSTRACT

Transscleral delivery of triamcinolone acetonide into the vitreous using sub-Tenon's injections may be a safer alternative to reduce the sight-threatening complications of direct intravitreal injections. However, sub-Tenon's injections have demonstrated low and poorly sustained vitreous drug levels in animal studies. To improve our understanding of the clearance mechanisms of corticosteroids, we evaluated vitreous drug levels following sub-Tenon's injection of triamcinolone acetonide in rabbits with selective elimination of conjunctival lymphatic/blood vessels and the choroid. Pigmented rabbits were given a sub-Tenon's injection of a preservative-free triamcinolone acetonide formulation of either a 10- or 20-mg dose in the superotemporal quadrant. The effect eliminating both conjunctival and choroidal clearance was evaluated by injecting the drug, followed by immediate euthanasia, effectively terminating both lymph and blood flow in the conjunctiva and choroid. To inhibit only the clearance from conjunctival lymphatics/blood vessels of a sub-Tenon's injection of triamcinolone acetonide, a group of rabbits had a 'conjunctival window' created by incising an 7 mmx7 mmx7 mm square through the conjunctiva to bare sclera in the superotemporal quadrant. To eliminate only the clearance of drug from the choroidal circulation, cryotherapy was performed in another group of rabbits creating a chorioretinal scar in the superotemporal quadrant. Following the sub-Tenon's drug injection, the eyes were enucleated in all groups after 3 hr and vitreous drug levels were measured with HPLC. In normal animals, a 10-mg sub-Tenon's injection showed no detectable vitreous drug levels; however, a 20-mg injection showed positive vitreous drug levels. This suggested that collectively, the transscleral clearance mechanisms inhibiting delivery into the vitreous may be saturated with a drug depot that has a higher release rate. A 10-mg sub-Tenon's drug depot was able to deliver drug into the vitreous when both the conjunctival and choroidal drug clearance was eliminated by euthanizing the animal immediately following the drug injection. In rabbits that had only a 'conjunctival window', selectively eliminating conjunctival drug clearance, vitreous drug levels were detected. However, in rabbits that had only cryotherapy, selectively eliminating choroidal drug clearance, vitreous drug levels were not detected suggesting that the conjunctival lymphatics/blood vessels may be an important barrier to the transscleral delivery of triamcinolone acetonide. Variability in the vitreous drug levels between rabbits in each group precluded statistical testing. In summary, the rabbit appeared to demonstrate saturable ocular barriers to transscleral delivery of triamcinolone acetonide into the vitreous following a sub-Tenon's injection. The results suggested that the conjunctival lymphatics/blood vessels may be an important barrier to the delivery of triamcinolone acetonide to the vitreous in this rabbit model. The barrier location and clearance abilities of the ocular tissues are important to consider when developing a successful transscleral drug delivery system. Animal models, retaining the dynamics of blood and lymph flow, may improve the basic understanding of the ocular barriers involved with transscleral drug transport and warrants further investigation.


Subject(s)
Glucocorticoids/pharmacokinetics , Sclera/metabolism , Triamcinolone Acetonide/pharmacokinetics , Vitreous Body/metabolism , Animals , Diffusion , Female , Glucocorticoids/analysis , Injections , Lymph/metabolism , Male , Rabbits , Sclera/chemistry , Triamcinolone Acetonide/analysis , Vitreous Body/chemistry
17.
J Pharm Biomed Anal ; 40(5): 1273-80, 2006 Mar 18.
Article in English | MEDLINE | ID: mdl-16297589

ABSTRACT

A high-performance liquid chromatography (HPLC) method with UV detection at 232 nm was developed and validated for the simultaneous determination of triamcinolone acetonide (TAA) and oxymetazoline hydrochloride (OXY) in nasal spray formulations. The chromatographic system consisted of a micro Bondapak CN column (150 mm x 3.9 mm), 5 microm particle size with a mobile phase composition of acetonitrile:ammonium acetate (pH 5.0, 20mM) (10:90, v/v) at a flow rate of 1.0 mL/min. Calibration curves were linear for both TAA and OXY in the concentration range of 2.5-25.0 microg/mL. The limit of detection and quantitation were 0.29 and 0.88 microg/mL for OXY and 0.24 and 0.73 microg/mL for TAA. The described method was further applied to the analysis and stability studies of two nasal spray formulations I and II prepared from TAA and OXY commercial nasal spray products. The stability of OXY and TAA in the commercial products and the nasal formulations I and II were analyzed after 30 days at room temperature and 30 days at 40 degrees C/60% relative humidity. The results of the stability study showed that OXY and TAA in the commercial nasal spray products and the nasal formulations I and II were stable at 20-25 degrees C (room temperature) but TAA was unstable at 40 degrees C/60% relative humidity. TAA exhibited more than 10% loss at 14 days in both the nasal formulations and in the commercial products. OXY showed increased degradation at 40 degrees C/60% relative humidity but <10%.


Subject(s)
Anti-Inflammatory Agents/analysis , Nasal Decongestants/analysis , Oxymetazoline/analysis , Triamcinolone Acetonide/analysis , Administration, Intranasal , Aerosols , Chemistry, Pharmaceutical , Chromatography, High Pressure Liquid , Drug Stability , Indicators and Reagents , Reference Standards , Reproducibility of Results , Solutions
18.
Jpn J Ophthalmol ; 49(5): 384-7, 2005.
Article in English | MEDLINE | ID: mdl-16187038

ABSTRACT

PURPOSE: Intravitreal injection of triamcinolone acetonide (TA) is used in ophthalmic treatment, but the reliability of commercially available TA preparations has still not been established. We evaluated two previously reported purification methods, and developed a more reliable TA injection which can be prepared in a hospital pharmacy. METHODS: We tested the two methods previously reported for purifying commercial TA preparations, the sedimentation and the filtration and backflushing methods. We developed a new TA injection made of pure TA suspended in 0.5% sodium hyaluronate. We measured the TA content in each preparation by high-performance liquid chromatography to evaluate the three methods. RESULTS: In the sedimentation purification method, the TA content of a nominal 4-mg preparation varied from 1.43 to 7.37 mg, and the average recovery rate was 91.6%. In the filtration and backflushing method, TA content was 0.10-10.33 mg and recovery was 59.5%. In the TA injection we developed, the mean TA content was 102.5% (SD, 0.24; CV, 2.9%). The stability of this preparation was 99% after sterilization, and 97% after 3 months of storage. CONCLUSIONS: The results of our investigation showed that the purification methods used for commercial preparations are simple and easy but not precise enough for an intravitreal injection. In contrast, the TA injection prepared by our method is reliable, stable, and safe enough for clinical use.


Subject(s)
Glucocorticoids/isolation & purification , Ophthalmic Solutions/isolation & purification , Triamcinolone Acetonide/isolation & purification , Chromatography, High Pressure Liquid , Glucocorticoids/analysis , Glucocorticoids/chemistry , Humans , Injections , Ophthalmic Solutions/analysis , Ophthalmic Solutions/chemistry , Triamcinolone Acetonide/analysis , Triamcinolone Acetonide/chemistry , Vitreous Body
19.
Am J Ophthalmol ; 139(4): 712-3, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15808171

ABSTRACT

PURPOSE: To determine the amount of triamcinolone acetonide and the preservative benzyl alcohol after filtration. DESIGN: Laboratory investigation. METHODS: The probes were prepared by two different hospital pharmacies. The probes of the first pharmacy included 20 probes with 25-mg triamcinolone acetonide, unfiltered (n = 5 probes) or filtered (n = 5), or with 4-mg triamcinolone acetonide, filtered (n = 5) or unfiltered (n = 5). The probes for the second pharmacy were filtered (n = 3) probes of 25-mg triamcinolone acetonide. RESULTS: For the probes of the first pharmacy, triamcinolone acetonide dosages were 2.4 +/- 0.8 mg, 3.1 +/- 0.6 mg, 12.8 +/- 0.7 mg, and 23.4 +/- 2.3 mg, respectively, for the filtered 4-mg probes, unfiltered 4-mg probes, filtered 25-mg probes, and unfiltered 25-mg probes, respectively. For the second pharmacy, mean triamcinolone acetonide dosage was 23.8 +/- 0.6 mg for the 25-mg filtered probes and contained benzyl alcohol in a mean concentration of 0.0013 +/- 0.0001 mg/0.1 ml. CONCLUSIONS: Depending on the method employed and the pharmacy, preparation of triamcinolone acetonide including filtration of the solvent agent leads to a marked inter-pharmacy variation and a relatively low intra-pharmacy variation in the reduction of triamcinolone acetonide dosage.


Subject(s)
Benzyl Alcohol/analysis , Filtration/methods , Glucocorticoids/analysis , Pharmaceutical Preparations/standards , Preservatives, Pharmaceutical/analysis , Triamcinolone Acetonide/analysis , Chromatography, High Pressure Liquid , Pharmacy Service, Hospital/standards
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