Question

It has been quite difficult if not impossible to produce nanoparticles from organic materials (especially for medicine) like Ibuprofen, aspirin, etc. since they aggregate at normal conditions. Propose a possible method of producing nano ibuprofen and nanoaspirin and explain why that is more feasible than other methods. Please be as much quantitative in your proposal as possible.

Answer 1

I am working in this field from last two years. I can not provide you exact procedure as it is matter of confidentiality , but I can provide you quite generalized procedure.

Preparation of Ibuprofen Nanoparticles

Ibuprofen nanoparticles were prepared by using solvent/antisolvent precipitation technique as an effective technology in preparation of nanodrugs. A certain amount of raw drug of ibuprofen was completely dissolved in water miscible solvent. At this work, the isopropyl alcohol is used as solvent. According to USP, isopropyl alcohol is categorized in Class 3. Class 3 includes no solvent known as a human hazard at levels normally accepted in pharmaceuticals.

However there are no long-term toxicity or carcinogenicity studies for many of the residual solvents in Class 3. The obtained drug solution was then injected into the water containing the surfactant of SDS and/or TEA as stabilizer under stirring at 3000 rpm. Precipitation of solid drug particles occurred immediately upon mixing. The suspension was centrifuged at 15,300 rpm for 20 min and washed twice with purified water. The precipitated nanoparticles were oven-dried at 35 oC for 24 h. The influence of other stabilizers such as polyvinyl pyrolidone (PVP), sodium lauryl sulfate (SLS) and tween 80 was also studied in the proposed procedure.

Solvent/ antisolvent precipitation technique was employed to produce nanoparticles of ibuprofen, a poorly water-soluble drug, for the enhancement of solubility.

Preparation of Aspirin Nanoparticles

Aspirin is chemically identical to the salicylic acid; which is a well known analgesic, anti-inflammatory and antipyretic drug. It is one of the popular Non steroidal Anti-inflammatory Drugs (NASIDs) and prescribed widely all over the world. It has attracted the attention due to its efficiency in the anti-platelet therapy for maintaining vessel potency in patients after undergoing coronary artery bypass grafting or angioplasty . A wide spectrum of literature is available on Aspirin . The first satisfactory mechanism for the action of this drug was proposed by Vane . The most common adverse effect of this drug is gastrointestinal disturbances such as, nausea, dyspersia and vomiting .

For any micro-emulsion it is first required to construct the phase diagram. At room temperature, a phase diagram for the AOT/n-heptane/water system was constructed by varying their concentrations in a step wise manner and a single phase region was determined. A limpid solution was obtained for the single phase region. The single phase region was used to obtain the micro-emulsion of Aspirin nano-particles.

The surfactant AOT was dissolved into the oil phase of n-heptane and then the desired amount of water was added to maintain [water] / [surfactant] molar ratio within the single phase region [21]. After the addition of water, the mixture was treated with continuous magnetic stir ing until a limpid solution was obtained and, thereafter, the solution of Aspirin in chloroform was added in a drop-wise manner.

Finally, the system was again treated with magnetic stirrer for 15 - 20 minutes. Treatments with stirring were necessary to give the energy to the system to speed up the formation of the reverse micelles. The micro-emulsion with Aspirin nano-particles was used for further characterization.