Salicylic acid particle size

T.R.M. De Beer, W.R.G. Baeyens, Y. Vander Heyden, J.R Remon, C. Vervaet and F. Verpoort, Influence of particle size on the quantitative determination of salicylic acid in a pharmaceutical ointment using FT-Raman spectroscopy, Em J. Pharm. Sci., 30, 229-235 (2007). 

Reactive crystallization, or precipitation, has been investigated by numerous research groups. Processes of industrial relevance include liquid-phase oxidation of para-xylene to terephthalic acid, the acidic hydrolysis of sodium salicylate to salicylic acid, and the absorption of ammonia in aqueous sulfuric acid to form ammonium sulfate (60). A very special type of reactive crystallization is diastereomeric crystallization, widely applied in the pharmaceutical industry for the resolution of enantiomers (61). Another fine example of reactive precipitation is the earlier-described production of nano-size particles of CaC03 in high-gravity fields (46). 

Modelling of the aerosol formation predicts that the particles produced in partial expansions are small, in the submicron range (5-6). However, experimental size are usually larger, indicating that growth or agglomeration occur within the free jet. Indeed, the temperature of the expansion chamber was found to be a sensitive parameters runs 105/140, 104/137 for anthracene, 147/149/148 for caffeine, 130/131 for salicylic acid show that the lower the temperature, the smaller are the particles. 

The effect of pressure is illustrated through runs 137/138, or 104/105, or 106/108 for anthracene, 76/78/80 or 85/147/159 for caffeine, 122/123 or 134/135 for salicylic acid. An increasing pressure leads to a decreasing size of particle, wether the solute concentration in the fluid is kept constant or varies with the pressure. In order to investigate the respective role of the pressure or the mole fraction on the particle size, further experiments and computational works are currently performed. 

Crystal growth of an industrially manufactured salicylic acid (9) powder (60 jt/m stated particle size) was demonstrated. A microscopic examination about eight months after its preparation showed a maximum particle size of 200-500 fjm. About one year later, examination showed further crystal growth, particle size now was 500-800 pm. A further examination after eight months showed no further particle size growth. Particle size growth of salicylic acid occurred even in the dry powder state and not only in ointments. 

The extraordinary photocatalytic performance of AEROXIDE TiOj P 25 in comparison to other nanoscaled titania particles has been published in several papers It is, for example, useful in the degradation of humic acid [71], of phenol and salicylic acid [72], of l,4dichlorobenzene [73], and in the photocatalytic reduction of Hg(II) [74]. It is also used in the oxidation of primary alcohols to aldehydes [75] or in the photopolymerization of methyl methacrylate [76]. Its use in cement can help reduce environmental pollution [77, 78]. A detailed study is reported by Bolte [79]. The results show that crystal size and filling ratio in mass are more important than the modification of the titania. Pyrogenic titania is not only useful in photocatalysis but also in other catalytic applications. 

For a good therapeutic effect the choice of the active substance and the choice of the vehicle are important. Physical and chemical factors play an important role. The solubility of the active substance in the vehicle and the concentration, the size of the molecule of the active substance, the partition between vehicle and skin, the particle size (in case of suspensions) and the nature of the vehicle (aqueous or lipid) determine the penetration speed and depth. Hydrocortisone, for example, is more lipid soluble in the ester form (hydrocortisone acetate). The latter will penetrate into the skin faster and more complete. Hydrocarbons, such as soft and liquid paraffin, release lipophilic active substances only very slowly and substances formulated in these bases will penetrate only in limited amounts into the skin. Fatty oils (vegetable oils, triglycerides) are able to pass into the upper layers of the skin. Penetration enhancers (salicylic acid, dimethyl sulfoxide, propylene glycol, urea) increase the penetration of active substances into the skin. 

Other studies investigated the incorporation of active molecules without a functionalization step. For example, supercritical CO2 was employed to impregnate the core of the PNBE-PEO particles with salicylic acid [35, 36]. Another variation consisted of adding a di-norbornenyl molecule 19 (Scheme 2.6) to the monomer-macromonomer mixture to obtain cross-linked nanoparticles by dispersion ROMP [37]. Reticulated polymer particles are interesting nanocarriers for the controlled release of encapsulated active substances. Raspberry-shaped nanoparticles in the size range of 300-600 nm were obtained, which arose from a double nucleation mechanism. NBE and the cross-linker were rapidly copolymerized in the first minutes of the reaction to afford a first population of highly cross-fiked particles, thereby preventing the incorporation of new active chains inside. A second population of particles was created subsequently from the... 

The catalytic efficiency of the Ti02/montmorillonite was tested on the photooxidation of salicylic acid. A photocatalyst suspension (0.1 wt/vol%) was prepared in 0.15 mM salicylic acid solution. Irradiations for 1 h were performed and samples were withdrawn after 5, 10, 20, 30,40, 50 and 60 min irradiation. Aliquots of the samples irradiated for various durations were centrifuged and particles interfering with photometry were removed by filtration through a sieve with 0.2 ptm pore size. Changes in salicylic acid concentration taking place as the reaction progressed were monitored by spectrophotometry at 297 nm (Fig. 3). The initial equilibrium concentration of salicylic acid was lowered by the adsorption of molecules on the oxide surface before irradiation [see the difference... 

Table 9.5 Increase of average particle size (d = 45 m) of salicylic acid within 10 days in non-aqueous media...

---