Synthesis and Formulation of Ibuprofen Pro-Drugs for Enhanced Transdermal Absorption (original) (raw)
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International Journal of Pharmacy and Pharmaceutical Sciences, 2015
Objectives: The aim is to synthesize ibuprofen prodrugs that have more suitable physicochemical properties and formulate them into a liquid formulation for topical administration. The transdermal delivery (TDD) is one of the most attractive routes for drug administration as it eliminates the GIT absorption variable, improves patient compliance and also reduces drug plasma fluctuations. However, TDD only drugs with suitable physico-chemical properties can be absorbed. The oral administration of NSAIDs for a long time can cause gastric mucosal damage, which may result in ulceration and bleeding. Thus, the development of a TDD of NSAIDs is of great interest as it decreases GIT side effects Methods: The synthesis of ibuprofen alkyl esters was carried out by esterification reactions with methanol, ethanol, propanol, butanol, pentanol and hexanol. The formulated samples were then subjected to stability studies according to ICH guidelines. Results: We have successfully synthesized and characterized various esters of ibuprofen. Moreover, ibuprofen butyl ester has been prepared as topical solutions. The formulated TDD was tested for stability according to ICH guidelines and the results showed no changes in the initial appearance during three months of study at room temperature & at 40 °C. Conclusion: The assay and pH were within the pharmacopeial limits during the period of the study. In conclusion, stable topical formulation of Ibuprofen esters was obtained.
Influence of selected formulation factors on the transdermal delivery of ibuprofen
2012
CHAPTER 2 MATERIALS AND METHODS 2.1 INTRODUCTION 2.2 MATERIALS 2.3 PREPARATION OF BUFFER SOLUTIONS 2.3.1 PREPARATION OF PHOSPHATE BUFFER SOLUTION (pH 7.4) 2.3.2 PREPARATION OF PHOSPHATE BUFFER SOLUTION (pH 5) 2.4 HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC METHOD VALIDATION 2.4.1 CHROMATOGRAPHIC APPARATUS AND CONDITIONS 2.4.2 PREPARATION OF STOCK SOLUTION
Formulation and Evaluation of Organo-Transdermal Gel of Drug Ibuprofen
International Journal of Pharmaceutical Sciences and Medicine
The current research project is centered on the development and assessment of an Ibuprofen topical gel made with Guar gum as the polymer and Carbopol 940 as a penetration enhancer. [ Gels were made by dispersing the polymers in a solution of guar gum and isopropyl myristate, along with Carbopol 940, glycerol as aqueous agents, and potassium sorbate as preservative, and different concentrations of ibuprofen, all while maintaining magnetic stirring. Triethanolamine was then added to the dispersion to neutralize it and make it viscous. Ibuprofen - Guar gum gels were discovered to be homogeneous and to have adequate drug loading. All of the gel compositions' pH values fell within the range of neutral pH, which is suitable for skin. And it was discovered that the compositions' viscosity was suitable for topical use the drug content of the nine formulations was found in the range of 80% to 90% which shows efficient drug loading. The compatibility study showed that the major peaks ...
Formulation and Evaluation of Transdermal Topical Gel of Ibuprofen
Journal of Drug Delivery and Therapeutics, 2020
The present research work is based on the formulation and evaluation of topical gel of Ibuprofen where Carbopol 940 is used as the polymer. Gels were prepared by dispersing the polymers in a mixture of water and glycerol with methyl paraben as the preservative and the varying amount of ibuprofen, being kept under magnetic stirring until the homogeneous dispersion was formed. The dispersion was then neutralized and made viscous by the addition of triethanolamine. The Carbopol gels of Ibuprofen were found to be homogenous with good drug loading. The pH of all the gel formulations was found within the neutral pH range which is compatible with skin. And the viscosity of the formulations was found to be feasible for topical drug delivery. The drug content of the three formulations was found in the range of 87.56% to 90.45% which shows efficient drug loading. Results of In vitro drug release study showed that F5 formulation has better diffusion of drug through egg membrane and hence furt...
Physicochemical properties of chiral ibuprofen are significant to formulation scientists because its enantiomers and eutectics possess lower melting points than its racemate. The influence of these properties on transdermal formulation development, especially the relative effect of lowered melting point, on skin permeation must be carefully assessed to provide the most efficacious formulation. Thermodynamic properties and crystalline structures of the enantiomers, eutectics, and racemate of chiral ibuprofen were investigated by differential scanning calorimetry and X-ray powder diffraction. The effect of melting point lowering on membrane permeation rates was mathematically modeled. Model was validated by in vitro skin permeation experiments using different preparations of racemic ibuprofen, enantiomer, and eutectic. Both enantiomer and eutectic formed a two-phase liquid system containing an emulsifiable aqueous phase and an oily phase in the presence of aqueous isopropyl alcohol (aIPA). The eutectic emulsion had the highest permeation rate, a 2.21-fold increase in flux compared with saturated aIPA solutions of the racemate with a 2.03-fold increase in flux. Results from the two-phase liquid system supported those from the mathematical models, albeit somewhat lower, and confirmed their use in predicting maximum flux utilizing thermodynamic data. Study data also supported the idea that eutectic formation, for ibuprofen and probably other chiral drugs, may be one of the best ways to develop topical formulations for improved percutaneous absorption to avoid the use of permeation enhancers or synthetically modifying chemical structure.
Development and evaluation of ibuprofen transdermal gel formulations
Tropical Journal of Pharmaceutical Research, 2010
Purpose: To develop an ibuprofen transdermal gel with a capability for both topical and systemic drug delivery. Methods: Ibuprofen gel formulations, incorporating various permeation enhancers, were prepared using chitosan as a gelling agent. The formulations were examined for their in vitro characteristics including viscosity, pH and drug release as well as in vivo pharmacological activities. Carrageenan-induced rat paw oedema model was used for the evaluation of their analgesic and anti-inflammatory activities. A commercial ibuprofen gel product (Ibutop ®) was used as a reference. Results: The formulations containing 5 % of either menthol or glycerol as permeation enhancers gave drug release patterns comparable to that of the reference product. Propanol increased the apparent viscosity of the test gels to the same extent as that of the reference. Drug release from the formulations fitted best to the Higuchi model. A significant in vivo analgesic effect was produced by the test formulations containing 5 % menthol and 20 % propylene glycol and the effect was superior to that obtained with the reference product. However, no significant anti-inflammatory activity was exerted by any of the test gel formulations (p > 0.05). Conclusion: Ibuprofen gel preparations containing 5 % menthol and 20 % propylene glycol, respectively, exhibited pronounced analgesic activity and could be further developed for topical and systemic delivery of ibuprofen.
Pharmaceutics, 2023
The aim was to assess the suitability of three nano-based transdermal drug delivery systems con-taining ibuprofen: a nano-emulsion, a nano-emulgel, and a colloidal suspension with ibuprofen-loaded nanoparticles. Understanding the transdermal delivery of ibuprofen using nano-based drug delivery systems can lead to more effective pain relief and improved patient compliance. Characterization tests assessed the suitability of the developed drug delivery systems. Membrane release and skin diffusion studies, along with tape stripping, were performed to determine drug release and skin permeation of ibuprofen. In vitro cytotoxicity studies on HaCaT cells were con-ducted using MTT and neutral red assays to evaluate the safety of the developed drug delivery systems. Characterization studies confirmed stable drug delivery systems with ideal properties for transdermal delivery. Membrane release studies demonstrated the successful release of ibu-profen. In vitro skin diffusion experiments and tape stripping, detecting ibuprofen in the receptor phase, stratum corneum-epidermis, and epidermis-dermis, indicating successful transdermal and topical delivery. The in vitro cytotoxicity studies observed only minor cytotoxic effects on HaCaT cells, indicating the safety of the developed drug delivery systems. The investigation demonstrat-ed promising results for the transdermal delivery of ibuprofen using the developed drug delivery systems, which contributes to valuable insights that may lead to improved pain management strategies.
Synthesis of Naproxen pro-drugs for enhanced transdermal absorption
2014
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) such as Naproxen have been used for a long time for the treatment of acute and chronic inflammation conditions. However, the oral administration of NSAIDs for a long time can cause gastric mucosal damage, which may result in ulceration and bleeding. Therefore, the development of a transdermal drug delivery (TDD) system of NSAIDs is of a great interest as it decreases GIT side effect and provides a constant release of drug in a determined period of time. Moreover, one of the important parameters of TTD is improving the permeability of the drug through human skin, since the stratum corneum layer of the epidermis prevents the permeability of various drugs and the naproxen in particular. In this present paper, we have successfully synthesized and characterized various ester derivatives of naproxen (methyl, ethyl, propyl, butyl, pentyl and hexyl esters) that have more suitable physicochemical properties for TDD and the butyl ester derivative has been formulated into liquid formulation for topical administration. The formulation was tested for stability according to ICH guidelines. No change in the initial appearance was observed during three months of study at room temperature & at 40 °C. The assay and pH were within the international standard limits during the period of the study. So, stable topical formulation of naproxen ester has been obtained.
Journal of Pharmacy and Pharmacology, 2003
Thiolated derivatives of ibuprofen and its polyethylene glycol ester were synthesized via condensation of 2-mercaptoethyl ibuprofenate with carboxy-terminated polyethylene glycol. The release of ibuprofen from this polymeric prodrug has been studied under conditions simulating those encountered in the skin. The polymeric prodrug of ibuprofen was found to undergo pH-dependent hydrolysis, ranging from negligible hydrolysis at pH 4 to 23.9% hydrolysis at pH 8.5 (15% at pH 7.4) after 48 h at 37 °C. The polymer–drug conjugate was subjected to enzymatic hydrolysis in human plasma. The polymer showed considerable enzymatic hydrolysis (68% after 48 h). The results showed that the polymeric prodrug model of non-steroidal anti-inflammatory drugs (NSAIDs) described here can be used in topical formulations of NSAIDs. It is expected that the novel thiol derivative will have both enhanced transdermal penetration and stability to oxidation which make it a suitable candidate for transdermal formula...
DEVELOPING A NOVEL MICROEMULSION CONTAINING IBUPROFEN FOR TRANSDERMAL APPLICATION By
Transdermal Drug Delivery System (TDDS) nowadays is one of the most important topics to deliver certain drugs in a safe, efficient and sustained manner and to achieve the acceptance of the patient. Microemulsions (MEs) are known to be good drug delivery systems for transdermal application. The droplet size and rheological properties play a vital role in the quality of MEs. In this study, Non-ionic surfactants were used to formulate MEs containing ibuprofen. The MEs were characterized for their droplet size, poly disparity index (PDI), rheological properties. Furthermore, the flux of Ibuprofen was evaluated by Franz diffusion cell in-vitro over 24h where the penetrated amount of ibuprofen was estimated using high performance liquid chromatography (HPLC). The in-