Preparation and Anesthetic Properties of Propofol Microemulsions in Rats

Morey, Timothy E.; Modell, Jerome H.; Shekhawat, Dushyant; Grand, Todd; Shah, Dinesh O.; Gravenstein, Nikolaus; McGorray, Susan P.; Dennis, Donn M.

doi:10.1097/00000542-200606000-00013

Cited by 41 publications

(26 citation statements)

References 37 publications

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“…Like other phenolic compounds, propofol is a membrane irritant [6]. The DOI: http://dx.doi.org/10.21454/rjaic.7518.231.emf pain on injection has been linked to the free propofol drug concentration, or the amount of drug freely dissolved in blood [7,8]. After an injection of propofol, the free drug concentration local to the injection site is affected by two factors: the emulsified propofol begins to dissolve after injection into the blood [9], but the much more likely factor is the amount of propofol freely dissolved in the emulsion continuous phase immediately mixing with the bloodstream at the intravenous injection site.…”

Section: Introductionmentioning

confidence: 99%

Propofol emulsion-free drug concentration is similar between batches and stable over time

Damitz

Chauhan

Gravenstein

2016

Rom J Anaesth Int Care

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Despite their widespread use for anesthesia and sedation, propofol emulsions have several unresolved issues, including pain on injection, stability concerns, and propensity to support bacterial growth. Pain accompanying a propofol injection has been attributed to the amount of free as opposed to emulsified propofol in the blood, which can differ with the formulation. Emulsions are inherently unstable and subject to several types of destabilization, but the actual mechanism may vary between formulations or batches. Free drug concentration and emulsion stability have not been widely studied between batches of propofol emulsions. Verifying whether batch-to-batch variability is a contributing factor to pain on injection or emulsion destabilization will help us better assess the causes and guide the design of future propofol formulations.Methods. Several samples of generic 1% propofol emulsion from various batches were compared. Free drug concentration was measured using an equilibrium dialysis method. Emulsion stability was evaluated by visible observation and by measuring droplet size distribution and polydispersity during shelf storage for up to 21 months.Results. Small differences in free drug concentration were observed between samples (10.6-16.7 μg/ mL), but these differences were not statistically significant (p > 0.05). Emulsion droplet size (235.4-221.1 nm) and polydispersity (0.115-0.095) did not differ statistically over 21 months of storage. All batches were resistant to creaming and other destabilization mechanisms.Conclusions. Batch-to-batch variability does not significantly alter the free drug concentration or stability of propofol formulations. If pain on injection of propofol is in fact related to the free propofol drug concentration, then it is unlikely that batch-to-batch variability causes any changes in pain on propofol injection.

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Section: Introductionmentioning

confidence: 99%

Propofol emulsion-free drug concentration is similar between batches and stable over time

Damitz

Chauhan

Gravenstein

2016

Rom J Anaesth Int Care

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“…A nanoemulsão é caracterizada por ser transparente, incolor e termodinamicamente estável, com partículas medindo entre 10 e 50ηm (MOREY et al, 2006b). Os veículos nanoemulsionados são estéreis, apirogênicos, biocompatíveis, não irritantes e não hemolíticos (DATE & NAGARSENKER, 2008).…”

Section: Introductionunclassified

Farmacocinética do propofol em nanoemulsão em cães

et al. 2013

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RESUMO O propofol em nanoemulsão é uma nova formulação constituída por sistemas nanoemulsionados, caracterizado pela ausência do veículo lipídico. A modifi cação do veículo pode 2, 5, 10, 15, 30, and 60 minutes after the bolus dose, and after the end of the infusion at fi ve, 10, 15, 30, 60, and 90 minutes and 2, 3, 4, 6, 10, and 24 hours. There were no signifi cant differences in the evaluated pharmacokinetics parameters that included volume of distribution, clearance, elimination rate constant, half-life, and distribution constants, demonstrating that propofol nanoemulsion has no pharmacokinetics differences when compared to the traditional formulation.

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“…Sodium caprylate (C 8 fatty acid) has been shown to cause significant hemolysis at a concentration of 213 mM (19). Although the microemulsions reported by Morey et al (18) do not contain such a high concentration of sodium caprylate, blood compatibility and parenteral acceptability of sodium salts of C 8 , C 10 and C 12 fatty acids on long term administration have not been established. Ryoo et al (20) in another investigation have reported formulation of microemulsion based on the Solutol ® HS 15 and ethanol.…”

Section: Introductionmentioning

confidence: 99%

Design and Evaluation of Microemulsions for Improved Parenteral Delivery of Propofol

Date

Nagarsenker

2008

AAPS PharmSciTech

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Abstract. The objective of this investigation was to evaluate the potential of the microemulsions to improve the parenteral delivery of propofol. Pseudo-ternary phase diagrams were plotted to identify microemulsification region of propofol. The propofol microemulsions were evaluated for globule size, physical and chemical stability, osmolarity, in vitro hemolysis, pain caused by injection using rat paw-lick test and in vivo anesthetic activity. The microemulsions exhibited globule size less than 25 nm and demonstrated good physical and chemical stability. Propofol microemulsions were slightly hypertonic and resulted in less than 1% hemolysis after 2 h of storage with human blood at 37°C. Rat paw-lick test indicated that propofol microemulsions were significantly less painful as compared to the marketed propofol formulation. The anesthetic activity of the microemulsions was similar to the marketed propofol formulation indicating that they do not compromise the pharmacological action of propofol. The stability studies indicated that the microemulsions were stable for 3 months when stored at 5±3°C. Thus, microemulsions appeared to be an interesting alternative to the current propofol formulations.

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Preparation and Anesthetic Properties of Propofol Microemulsions in Rats

Cited by 41 publications

References 37 publications

Propofol emulsion-free drug concentration is similar between batches and stable over time

Propofol emulsion-free drug concentration is similar between batches and stable over time

Farmacocinética do propofol em nanoemulsão em cães

Design and Evaluation of Microemulsions for Improved Parenteral Delivery of Propofol

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