Indomethacin dissolution

The interaction between drug compounds and excipients, as these influence drug dissolution, can be successfully studied by means of reflectance spectroscopy. In one study concerning probucol and indomethacin, it was deduced that hydrogen bonding and van der Waals forces determined the physisorption between the active and the excipients in several model formulations [36]. Chemisorption forces were found to play only minor roles in these interactions. These studies indicated that surface catalytic effects could be important during the selection of formulation excipients. 

Ramtoola Z, Corrigan 01. Effect of agitation intensity on the dissolution rate of indomethacin and indomethacin-citric acid compressed discs. Drug Dev Ind Pharm 1988 14(15-17) 2241-2253. 

The combination of solid-state ATR-IR and solid-state NMR data supported the conclusion that the presence of crystalline material was responsible for changes in the dissolution profiles of the different lots. The results appear consistent with historical examples of changes in API physical form of solid, high molecular weight, polyethylene glycol dispersion formulations of amorphous indomethacin and griseofulvin (92-95). 

Fini, A., Holgado, M., Rodriguez, L., and Cavallari, C., Ultrasound-compacted indomethacin/polyvinylpyrrolidone systems Effect of compaction process on particle morphology and dissolution behavior, Journal of Pharmaceutical Sciences, Vol. 91, No. 8, 2002, pp. 1880—1890. 

Matsuda Y, Kouzuki K, Tanaka M, Tanigaki J. Photostability of gelatin capsules effect of ultraviolet irradiation on the vapor transmission properties and dissolution rates of indomethacin. Yakugaku Zassi 1979 99(9) 907-913. 

Irradiation of gelatine capsules may not only result in photodegradation of the drug but may also affect the bioavailability of the drug. Irradiated gelatine films showed a decrease of their water vapor transmission. Even though this effect did not occur with indomethacin capsules, long-term irradiation resulted in increased dissolution rates (42). 

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. ... 

An IVIVC correlation was tried on indomethacin suppositories containing either suppocire (lipophilic) or poly ethylene glycol(PEG hydrophilic) as the main excipient. For both formulations, in vitro dissolution was performed with USP IV apparatus and a correlation was attempted, the results of the intrinsic validation are presented in Fig. 12 and show good predictability of the plasma concentrations in both cases. 

One problem with many of the active substances used today is their poor solubility in water and their limited bioavailability. One of the simplest means of improving the bioavailability of an active substance is to improve its dissolution by adding solubilizing agents, such as povidone. It forms water-soluble complexes with many active substances (see Sections 2.2.7 and 2.4.5). With some such substances, it may be sufficient to produce a physical mixture. Fig. 45 shows the improvement in the dissolution rate of reserpine achieved by simply mixing it with an excess of povidone K 30. For the mixture with indomethacin see Section 3.4.3.1. Similar results can be expected with the drugs listed in Section 2.4.5. That this effect also applies to finished preparations can be seen for phenytoin tablets in Fig. 52 [326]. The bioavailability of peroral gidazepam is increased by the addition of povidone too [536]. 

It is interesting to note that, although crospovidone is insoluble, it can be used in solid pharmaceutical preparations to improve the dissolution rate of an active substance. That this is not merely the result of a short-term increase in the surface area of the active substance but of the formation of a complex, can be seen in Fig. 80. Simply mixing indomethacin with crospovidone multiplies the dissolution rate of this drug substance during more than two hours. Similar results were obtained with indoprofen [439],propyphenazone [426] and prostaglandin ester [359]. 

Furthermore Fig. 80 shows that povidone and crospovidone increase in a comparable way the dissolution of indomethacin forming the same complex between drug and polymer. As the particle size and the swelling of these two polmers is quite different, this could explain the slight difference of dissolution. 

Fig. 80. Improvement of the dissolution fo indomethacin in water at 25°C mixing with crospovidone or povidone...

Debenedetti and coworkers (88,89) provided one of the first examples of microencapsulation of a drug in the polymeric matrix. Richard and coworkers (90) provided a recent example of the microencapsulation process when they produced microparticles with the encapsulated model protein that showed sustained release. Foster and coworkers (87) also reported precipitation of copper-indomethacin by PVP with a 96-fold enhancement in the dissolution rate of indomethacin. These examples clearly demonstrated the advantages of using supercritical fluid processing for the preparation of polymer-drug formulations with potentially improved therapeutic properties. 

An example of precipitation in the presence of a second solvent is seen in the case of indomethacin. The y-crystal form of indomethacin can be obtained by recrystallization from ethyl ether at room temperature, but the a-form is prepared by dissolution in methanol and precipitation with water at room temperature [33], Precipitation can also result from the addition of a less polar solvent. Form II of midodrine hydrochloride, metastable with respect to Form I, can be prepared by precipitation from a methanolic solution by means of a less polar solvent such as ethyl acetate or dichloromethane [34],... 

Chowdary, K.P.R., Babu, K. Dissolution, bioavaUabUity and ulcerogenic studies on solid dispersions of indomethacin in water-soluble cellulose polymers. Drug Dev. Ind. Pharm. 1994, 20(5), 799—813. 

Shakeel, E., Haq, N., El-Badry, M., Alanazi, E.K., Alsarra, I.A., 2013. Ultra fine super self-nanoemulsifying drug delivery system (SNEDDS) enhanced solubility and dissolution of indomethacin. J. Mol. Liq. 180, 89—94. 

Indomethacin (l-(p-chlorobenzoyl)-5-methoxy-2-methyIindole-3-acetic acid, IMC), can exist in several crystalline forms (e.g., a-, y-, and 8-polymorphs and others) [34, 62], Due to the poor water solubility of the most stable y-foim [63], IMC has been a popular choice as a model compound to explore the benefits of amorphous solid dispersions for enhancing solubility [64], thereby improving dissolution rates and oral bioavailability [65]. 

In vitro dissolution of drugs from suppositories P or this study suppositories of different suppository bases were prepared by using free and (3-cyclodextrin complexed fennel oil and indomethacin. 

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