Indomethacin solubility

Once the indomethacin forms are available, seeding a crystallization batch with the desired form will usually result in the isolation of that form. When excess solid Form II and Form III, either individually or as a mixture, are stirred (agitated, equilibrated) in most solvents and for sufficient time, they convert to the more stable Form I. The time to conversion is roughly related to solubility conversion time is faster for the solvents with higher indomethacin solubility. In water (Table 3-1), where the solubility is relatively low. Form n and Form III of indomethacin did not convert even after 24 hours of stirring. 

Industrial and Engineering Chemistry Research 43, No.4, 18th Feb.2004, p. 1103-12 INCREASING COPPER INDOMETHACIN SOLUBILITY BY COPRECIPITATION WITH POLY(VINYLPYRROLIDONE) USING THE AEROSOL SOLVENT EXTRACTION SYSTEM Meure LA Warwick B Dehghani F Regtop H L Foster N R... 

Figure 6.1 Solubility-pH profile (a) and a log-log speciation plot (b) for a weak acid (indomethacin, pKa 4.42, log So —5.58 [pION]). [Avdeef, A., Curr. Topics Med. Chem., 1, 277-351 (2001). Reproduced with permission from Bentham Science Publishers, Ltd.]...

In addition to potassium phenoxymethylpenicillin (aqueous solubility >10 mg/mL except at low pH), which just fails to meet the BCS criteria for highly soluble at higher doses, there are numerous other examples of compounds which are unable to meet the criteria at low pH but which fall well within the required D S range at typical pH in the small intestine. Notable examples include ibuprofen and indomethacin,... 

Replacing the 5-MeO substituent of indomethacin with a Me2N group produced a compound with higher water solubility. This analogue (MK-825, 4.96) was extensively metabolized (ca. 40% in humans) by hydrolysis to 4-chlorobenzoic acid, which was excreted in the urine as 4-chlorobenzoylgly-cine [59]. 

Watanabe, K., et al. 1993. Investigation on rectal absorption of indomethacin from sustained-release hydrogel suppositories prepared with water-soluble dietary fibers, xanthan gum and locust bean gum. Biol Pharm Bull 16 391. 

A pKa of 4.5 for the carboxyl group of indomethacin was calculated from aqueous solubility data(30). Potentiometric titration data for indomethacin in 50% methanol-water yielded pKa of 4.5 using a correction factor for the solvent(31). 

Figure 6.17 The classification of 42 drugs in the (solubility-dose ratio, apparent permeability) plane of the QBCS. The intersection of the dashed lines drawn at the cutoff points form the region of the borderline drugs. Key 1 acetyl salicylic acid 2 atenolol 3 caffeine 4 carbamazepine 5 chlorpheniramine 6 chlorothiazide 7 cimetidine 8 clonidine 9 corticosterone 10 desipramine 11 dexamethasone 12 diazepam 13 digoxin 14 diltiazem 15 disopyramide 16 furosemide 17 gancidovir 18 glycine 19 grizeofulvin 20 hydrochlorothiazide 21 hydrocortisone 22 ibuprofen 23 indomethacine 24 ketoprofen 25 mannitol 26 metoprolol 27 naproxen 28 panadiplon 29 phenytoin 30 piroxicam 31 propanolol 32 quinidine 33 ranitidine 34 salicylic acid 35 saquinavir 36 scopolamine 37 sulfasalazine 38 sulpiride 39 testosterone 40 theophylline 41 verapamil HC1 42 zidovudine.

The mechanism of the drug release appeared to be simple diffusion from an EC matrix tablet and the data could be adequately described by the Higuchi square root of time relationship for water-soluble pseudophedrine hydrochloride at 12.5-25 % drug loading [309]. Release of the slightly soluble theophylline or the practically insoluble indomethacin from such tablets at 50 % or 25 % drug loading, respectively, was described by diffusion with polymer relaxation and erosion contributions to the release mechanism [313]. 

Assouline M, Renard G, Ame JL, David T, et al. A prospective randomized trial of topical soluble 0.1% indomethacin versus 0.1% diclofenac versus placebo for the control of pain foUowing excimer laser photorefractive keratectomy. Ophthalmic Surg Lasers 1998 29 365-374. 

Amorphous materials typically have a higher rate of dissolution and a higher kinetic solubility that their crystalline counterparts (Fig. 1). These characteristics can be exploited to enhance the rate and extent of absorption of poorly water-soluble APIs from the gastrointestinal tract. Such formulation approaches have been described for many APIs including indomethacin, griseofulvin, and several barbiturates. ... 

Fig. 1 Aqueous solubility of the amorphous and crystalline forms of indomethacin. (From Ref...

Crystallinity of the particles. For example, amorphous form of indomethacin is more soluble than the crystalline one. ... 

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