Salt formation during freeze-drying - an approach to enhance indomethacin dissolution

Thakral, Seema; Suryanarayanan, Raj
November 2015
Pharmaceutical Research;Nov2015, Vol. 32 Issue 11, p3722
Academic Journal
Purpose: (i) Prepare a freeze-dried injectable indomethacin (IMC) dosage form. (ii) Convert IMC to its tris salt during freeze-drying so as to facilitate rapid dissolution (reconstitution). (iii) Modulate salt crystallinity by annealing the frozen solution. Methods: Aqueous IMC solutions buffered with tris were freeze dried, with or without annealing the frozen solutions. The lyophiles were characterized by X-ray diffractometry, differential scanning calorimetry and infra-red spectroscopy and also subjected to water sorption and dissolution studies. Results: Based on IR spectroscopy, the final lyophile was confirmed to contain the IMC tris salt. In the absence of annealing, the lyophile was X-ray amorphous with a glass transition temperature of 19°C. Annealing the frozen solutions caused a substantial increase in lyophile crystallinity. Interestingly, both the amorphous and partially crystalline lyophiles dissolved 'instantaneously' and completely in the dissolution medium. In contrast, the crystalline IMC as well as its physical mixture with tris exhibited much slower dissolution with ~ 50% drug dissolved in 30 min. Conclusion: In situ IMC tris salt formation resulted in an elegant lyophile with a very short reconstitution time. Tris served two roles - as a buffer in the prelyophilization solution and as the counterion for the salt in the final lyophile. This approach for solubility enhancement could be extended to other acidic drugs wherein salt formation was observed during freeze-drying.


Related Articles

  • In-vitro Dissolution Rate Enhancement of Indomethacin with PEG 4000, Sodium benzoate, Niacinamide by solid Dispersion technique. Jain, Jitendra; Patani, Mital; Mathuria, Khemchand; Gupta, Vikas; Upadhyay, Navneet // Journal of Pharmacy Research;Oct2011, Vol. 4 Issue 10, p3386 

    The present investigation was to improve the solubility and dissolution rate of a poorly water soluble drug Indomethacin by using solid dispersion technique. To enhance the dissolution rate formulate solid dispersions using different solubilizers such as polyethylene glycol 4000, Sodium...

  • Preparation, Characterization and Stability Studies of Glassy Solid Dispersions of Indomethacin using PVP and Isomalt as carriers. Khodaverdi, Elham; Khalili, Noman; Zangiabadi, Farzad; Homayouni, Alireza // Iranian Journal of Basic Medical Sciences;May/Jun2012, Vol. 15 Issue 3, p820 

    Objective(s) The purpose of the present study was to use the solid dispersion (SD) technique to improve the dissolution rates of indomethacin (IMC). Materials and Methods IMC solid dispersions in PVP K30 and isomalt (GALEN IQ 990) were prepared using the solvent evaporation technique and a hot...

  • Influence of Processing Conditions on the Physical State of Mannitol—Implications in Freeze-Drying. Xiangmin Liao; Rajesh Krishnamurthy; Raj Suryanarayanan // Pharmaceutical Research;Feb2007, Vol. 24 Issue 2, p370 

    AbstractPurpose??To study the effect of processing conditions on the physical state of mannitol during various stages of the lyophilization cycle of a protein formulation.Materials and Methods??Mannitol and trehalose were used as the bulking agent and lyoprotectant, respectively. The physical...

  • Improvement in solubility of poor water-soluble drugs by solid dispersion. Sareen, Swati; Mathew, George; Joseph, Lincy // International Journal of Pharmaceutical Investigation;2012, Vol. 2 Issue 1, p12 

    This article is intended to combine recent literature on solid dispersion technology for solubility enhancement with special emphasis on mechanism responsible for the same by solid dispersion, various preparation methods, and evaluation parameters. Solubility behavior is the most challenging...

  • A NOVEL TECHNIQUE TO ENHANCING THE SOLUBILITY AND DISSOLUTION OF FLUTAMIDE USING FREEZE DRYING. DIXIT, Mudit; KINI, Ashwini G.; KULKARNI, Parthasarthi K.; SHIVAKUMAR, Hosakote Gurumallappa // Turkish Journal of Pharmaceutical Sciences;2012, Vol. 9 Issue 2, p139 

    Flutamide, an anticancer drug for prostatic carcinoma has poor aqueous solubility and low oral bioavailability. The study aims to enhance the aqueous solubility and dissolution of flutamide by developing a Flutamide freeze dried tablet (FDT). The FDT was prepared by dispersing the drug in an...

  • In vitro Evaluation of Acyclovir/Chitosan Floating Systems. Ruiz-Caro, Roberto; Veiga, María D. // Materials (1996-1944);Dec2010, Vol. 3 Issue 12, p5195 

    Chitosan (CS) floating lyophilized formulations (L) for gastric drug delivery of acyclovir (ACV) have been developed. The freeze-dried formulations were obtained from acidic aqueous suspensions prepared with different ACV/CS ratios. No changes in ACV crystallinity were observed during X-ray...

  • Liver Crude Phospholipid and In Vitro Calcification. ENNEVER, J.; BOYAN-SALYERS, B.; VOGEL, J. J. // Journal of Dental Research;May1977, Vol. 56 Issue 5, p539 

    The article reports on the calcifiability of crude phospholipid from fetal calf liver in vitro. A study was conducted using freeze-dried tissue which was treated with chloroform-methanol and crude phospholipid precipitated with acetone. Crude phospholipid were incubated in tubes with metastable...

  • Characterization and Antioxidant Activity of the Complex of Phloridzin and Hydroxypropyl-β-cyclodextrin. Erdong Yuan; Benguo Liu; Wei Li; Qiong Li // Tropical Journal of Pharmaceutical Research;Aug2012, Vol. 11 Issue 4, p545 

    Purpose: To improve the aqueous solubility of phloridzin by complexing it with hydroxypropyl-β- cyclodextrin (HP-β-CD). Methods: The complex of phloridzin with HP-β-CD was prepared by freeze-drying method. The physicochemical properties of the complex were investigated by...

  • Development and characterization of nanosuspensions of olmesartan medoxomil for bioavailability enhancement. Thakkar, Hetal Paresh; Patel, Bindesh Vishnubhai; Thakkar, Sneha Piyush // Journal of Pharmacy & Bioallied Sciences;Jul-Sep2011, Vol. 3 Issue 3, p426 

    Background: Olmesartan medoxomil (OLM), an anti-hypertensive agent administered orally has absolute bioavailability of only 26% due to the poor aqueous solubility (<7.75 μg/ml). The present investigation aimed at enhancing the oral bioavailability of OLM by improving its solubility and...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics