Stability and compatibility of admixtures containing bupivacaine hydrochloride and ketorolac tromethamine for parenteral use

2021 ◽  
pp. ejhpharm-2021-003003
Author(s):  
Hani Abdeltawab ◽  
Jagdish Kumar Jaiswal ◽  
Simon W Young ◽  
Darren Svirskis ◽  
Andrew Hill ◽  
...  
2018 ◽  
Vol 14 (5) ◽  
pp. 432-439 ◽  
Author(s):  
Juliana M. Juarez ◽  
Jorgelina Cussa ◽  
Marcos B. Gomez Costa ◽  
Oscar A. Anunziata

Background: Controlled drug delivery systems can maintain the concentration of drugs in the exact sites of the body within the optimum range and below the toxicity threshold, improving therapeutic efficacy and reducing toxicity. Mesostructured Cellular Foam (MCF) material is a new promising host for drug delivery systems due to high biocompatibility, in vivo biodegradability and low toxicity. Methods: Ketorolac-Tromethamine/MCF composite was synthesized. The material synthesis and loading of ketorolac-tromethamine into MCF pores were successful as shown by XRD, FTIR, TGA, TEM and textural analyses. Results: We obtained promising results for controlled drug release using the novel MCF material. The application of these materials in KETO release is innovative, achieving an initial high release rate and then maintaining a constant rate at high times. This allows keeping drug concentration within the range of therapeutic efficacy, being highly applicable for the treatment of diseases that need a rapid response. The release of KETO/MCF was compared with other containers of KETO (KETO/SBA-15) and commercial tablets. Conclusion: The best model to fit experimental data was Ritger-Peppas equation. Other models used in this work could not properly explain the controlled drug release of this material. The predominant release of KETO from MCF was non-Fickian diffusion.


2021 ◽  
pp. rapm-2020-102427
Author(s):  
Hanns-Christian Dinges ◽  
Thomas Wiesmann ◽  
Berit Otremba ◽  
Hinnerk Wulf ◽  
Leopold H Eberhart ◽  
...  

Background/ImportanceLiposomal bupivacaine (LB) is a prolonged release formulation of conventional bupivacaine designed for prolonging local or peripheral regional single injection anesthesia. To this day, the benefit of the new substance on relevant end points is discussed controversial.ObjectiveThe objective was to determine whether there is a difference in postoperative pain scores and morphine consumption between patients treated with LB and bupivacaine hydrochloride in a systematic review and meta-analysis.Evidence reviewRandomized controlled trials (RCT) were identified in Embase, CENTRAL, MEDLINE and Web of Science up to May 2020. Risk of bias was assessed using Cochrane methodology. Primary end points were the mean pain score difference and the relative morphine equivalent (MEQ) consumption expressed as the ratio of means (ROM) 24 and 72 hours postoperatively.Findings23 RCTs including 1867 patients were eligible for meta-analysis. The mean pain score difference at 24 hours postoperatively was significantly lower in the LB group, at −0.37 (95% CI −0.56 to −0.19). The relative MEQ consumption after 24 hours was also significantly lower in the LB group, at 0.85 (0.82 to 0.89). At 72 hours, the pain score difference was not significant at −0.25 (−0.71 to 0.20) and the MEQ ratio was 0.85 (0.77 to 0.95).ConclusionThe beneficial effect on pain scores and opioid consumption was small but not clinically relevant, despite statistical significance. The effect was stable among all studies, indicating that it is independent of the application modality.


Author(s):  
Pierre Diemunsch ◽  
Martine Alt ◽  
Anne-Marie Diemunsch ◽  
Alain Treisser

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 467
Author(s):  
Shahla S. Smail ◽  
Mowafaq M. Ghareeb ◽  
Huner K. Omer ◽  
Ali A. Al-Kinani ◽  
Raid G. Alany

Nanoemulsions (NE) are isotropic, dispersions of oil, water, surfactant(s) and cosurfactant(s). A range of components (11 surfactants, nine cosurfactants, and five oils) were investigated as potential excipients for preparation of ketorolac tromethamine (KT) ocular nanoemulsion. Diol cosurfactants were investigated for the effect of their carbon chain length and dielectric constant (DEC), Log P, and HLB on saturation solubility of KT. Hen’s Egg Test—ChorioAllantoic Membrane (HET-CAM) assay was used to evaluate conjunctival irritation of selected excipients. Of the investigated surfactants, Tween 60 achieved the highest KT solubility (9.89 ± 0.17 mg/mL), followed by Cremophor RH 40 (9.00 ± 0.21 mg/mL); amongst cosurfactants of interest ethylene glycol yielded the highest KT solubility (36.84 ± 0.40 mg/mL), followed by propylene glycol (26.23 ± 0.82 mg/mL). The solubility of KT in cosurfactants was affected by four molecular descriptors: carbon chain length, DEC, log P and HLB. KT solubility was directly proportional to DEC and the HLB yet, inversely proportional to carbon chain length and log P. All surfactants, except Labrasol ALF, were non-irritant. The majority of cosurfactants were slightly irritant, butylene glycol was a moderate irritant, pentylene and hexylene glycols were strong irritants. These findings will inform experiments aimed at developing NE formulations for ocular administration of KT.


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