Kinetics of Decomposition and Formulation of Hydrocortisone Butyrate in Semiaqueous and Gel Systems

Yip, Yue-Keung; Pox, A. Li Wan; Irwin, W. J.

doi:10.1002/jps.2600720715

Cited by 24 publications

(9 citation statements)

References 10 publications

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“…Lipophilic HB for the treatment of inflammation suffers from poor solubility, low bioavailability, and severe side effects. A few attempts to increasing dissolution and bioavailability of HB have met with limited success [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle-Based Topical Ophthalmic Gel Formulation for Sustained Release of Hydrocortisone Butyrate

et al. 2015

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Abstract. This study was conducted to develop formulations of hydrocortisone butyrate (HB)-loaded poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA NP) suspended in thermosensitive gel to improve ocular bioavailability of HB for the treatment of bacterial corneal keratitis. PLGA NP with different surfactants such as polyvinyl alcohol (PVA), pluronic F-108, and chitosan were prepared using oil-in-water (O/W) emulsion evaporation technique. NP were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential, and crystallinity. In vitro release of HB from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when nanoparticles were suspended in thermosensitive gels and zero-order release kinetics was observed. In HCEC cell line, chitosanemulsified NP showed the highest cellular uptake efficiency over PVA-and pluronic-emulsified NP (59.09±6.21%, 55.74±6.26%, and 62.54±3.30%, respectively) after 4 h. However, chitosan-emulsified NP indicated significant cytotoxicity of 200 and 500 μg/mL after 48 h, while PVA-and pluronic-emulsified NP exhibited no significant cytotoxicity. PLGA NP dispersed in thermosensitive gels can be considered as a promising drug delivery system for the treatment of anterior eye diseases.

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Section: Introductionmentioning

confidence: 99%

Nanoparticle-Based Topical Ophthalmic Gel Formulation for Sustained Release of Hydrocortisone Butyrate

et al. 2015

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“…However, the C21 esterification considerably lowers the capabil ity of the glucocorticoid to bind itself to the glucocorticoid receptor molecule and there fore makes the C21 glucocorticoid ester a 'prodrug', which requires the C21 hydrolysis for the realization of a sufficient biological activity. On the basis of the studies on intra dermal metabolism of corticoids, it has been established for human skin that this type of esterolytic reaction occurs in the skin [Pannatier et al, 1978;Cheung et al, 1985;Tauber and Rost, 1987], Alongside enzymatic ester hydrolysis, nonenzymatic conversions, especially of C l7 monoesters, can apparently also take place in the epidermis [Bundgaard and Hansen, 1981;Yip et al, 1983]. In contrast to this, halogen substituents, most often in position Cftalpha and Gjalpha, increase the affinity of the gluco corticoid molecule to the intracellular recep tor protein and thus lead to an increase in the intrinsic activity of the steroid on the one hand; on the other hand halogen substituents cause a delay of the systemic metabolism [Myles et al, 1957;Wolff, 1979].…”

Section: Discussionmentioning

confidence: 99%

Studies on the Pharmacokinetics and Metabolism of Prednicarbate after Cutaneous and Oral Administration

Barth

Lehr²,

Derendorf

et al. 1993

Skin Pharmacol Physiol

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Prednicarbate (PC) is a nonhalogenated derivative of prednisolone which is used for the local treatment of corticoid-sensitive skin diseases. In this study, the pharmacokinetics and the metabolism of PC in humans are investigated after cutaneous ointment application (75 mg PC) and after systemic oral administration (40 mg PC) in 8 healthy volunteers. In addition, the possible suppression of endogenous cortisol secretion by both application forms was monitored. After oral administration no intact PC, but significant levels of the first metabolite prednisolone-17-ethylcarbon-ate (PRED-17-EC) were determined. PRED-17-EC was further metabolized with a half life of 1.6 h to prednisolone. After percutaneous administration neither PC nor other known metabolites could be detected system-ically. The low systemic bioavailability after dermal application was also reflected in an unchanged cortisol secretion pattern. According to animal studies our metabolic studies in humans suggest that the prednisolone-17-ester PRED-17-EC, which has a receptor binding affinity comparable to that of dexamethasone is the pharmacologically active compound. As PRED-17-EC subsequently undergoes an inactivation step to the low active prednisolone this may be the reason for the dissociation of good local efficacy and low systemic side effects.

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“…The degradation of betamethasone and related corticosteroids has been the subject of many investigations in the form of solutions[6–9], solid state[610] and in various dosage forms[11–13]. The major degradation reactions encountered with these esters are oxidation[14–19] and ester group migration followed by hydrolysis[6–911121320–27]. These reactions are influenced by pH, solvent polarity, oxygen content and temperature[14–1720–25].…”

mentioning

confidence: 99%

“…The major degradation reactions encountered with these esters are oxidation[14–19] and ester group migration followed by hydrolysis[6–911121320–27]. These reactions are influenced by pH, solvent polarity, oxygen content and temperature[14–1720–25]. …”

mentioning

confidence: 99%

Kinetics of thermal degradation of betamethasone valerate and betamethasone dipropionate in different media

et al. 2012

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The effect of pH, media, phosphate concentration and ionic strength on the kinetics of thermal degradation of betamethasone valerate and betamethasone dipropionate has been investigated. A validated HPLC method has been used to determine the parent compounds and their major thermal degradation products identified in the reaction. Betamethasone-17-valerate gave rise to two major products, namely, betamethasone-21-valerate and betamethasone alcohol, and betamethasone dipropionate degraded into three major products, namely, betamethasone-17-propionate, betamethasone-21-propionate and betamethasone alcohol, in different media. Betamethasone valerate showed maximum stability at pH 4-5 while betamethasone dipropionate was maximally stable at pH 3.5-4.5. The degradation of betamethasone valerate and betamethasone dipropionate was found to follow first-order kinetics and the apparent first-order rate constants (kobs) for thermal degradation in different media range from 0.399-9.07×10-3 h-1 and 0.239-1.87×10-3 h-1, respectively. The values of the rate constants decrease with increasing solvent polarity, phosphate concentration and ionic strength. The second-order rate constants (k΄) for the phosphate ion inhibited reactions lie in the range of 3.02-1.30×10-6 M-1 s-1.

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Kinetics of Decomposition and Formulation of Hydrocortisone Butyrate in Semiaqueous and Gel Systems

Cited by 24 publications

References 10 publications

Nanoparticle-Based Topical Ophthalmic Gel Formulation for Sustained Release of Hydrocortisone Butyrate

Nanoparticle-Based Topical Ophthalmic Gel Formulation for Sustained Release of Hydrocortisone Butyrate

Studies on the Pharmacokinetics and Metabolism of Prednicarbate after Cutaneous and Oral Administration

Kinetics of thermal degradation of betamethasone valerate and betamethasone dipropionate in different media

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