Using Polymers to Enhance Solubility of Poorly Soluble Drugs - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

Using Polymers to Enhance Solubility of Poorly Soluble Drugs
The authors demonstrate how melt-extrusion and spray-drying methods can help to prepare solid dispersions of poorly soluble drugs using Eudragit polymers.


Pharmaceutical Technology


Results

For the spray-dried samples, the residual solvent content was measured by loss on drying with infrared (IR) spectroscopy. Less than 0.95 wt% of residual ethanol content in the spray-dried sample was found and presumed not to influence XRPD, DSC, or stability.


Figure 1 (All figures are courtesy of the authors.)
Spray-drying and melt extrusion with felodipine. In a previous study, 10% of felodipine was identified as the optimum drug load with respect to dissolution (3). Spray-dried samples, therefore, were produced with a 10% drug load and compared with the results of an extrudate with the same formulation used in a previous study (3). Spray-dried and extruded samples were analyzed with DSC and XRPD to evaluate the crystallinity of felodipine in the samples. In XRPD (see Figure 1), no typical peaks referring to felodipine could be observed in the spray-dried sample or in the extrudates. In comparison, the corresponding physical mixture showed peaks in XRPD at 10.23 (2θ), 10.88(2θ), 16.6(2θ), 20.5 (2θ) und 23.7(2θ), where θ is defined as the incident angle of the X-ray (i.e., the angle between the incident X-ray and the plane of the sample). Because Eudragit polymers are amorphous and the positions of the peaks are equal to pure felodipine, these peaks are clearly related to pure felodipine. Both methods lead to a formation of a solid dispersion of felodipine, Eudragit E and Eudragit NE 30 D.


Figure 2
These results were confirmed with DSC. The DSC runs of pure felodipine, a physical mixture, and the spray-dried and extruded samples can be seen in Figure 2. In the physical mixture and in the pure felodipine, a melting peak was detected, whereas in the spray-dried sample and in the extruded sample, no melting peak was observed. Only one glass transition temperature (T g) could be seen. The Tg value in the melt-extruded sample is below the Tg value of the pure polymer, meaning felodipine has a slightly plasticizing effect on the polymer. The appearance of a single Tg is an indication for the formation of a glassy solution where the drug is dissolved in the polymer.


Figure 3
The formation of a solid glassy solution leads increases the dissolution rate and apparent solubility of felodipine. In Figure 3, the solubility of the spray-dried sample is compared with the solubility of pure felodipine and the physical mixture. For felodipine, no solubility was detected because the value was below the detection limit. The physical mixture increased in solubility (40 µg/mL), because of to the wetting properties of Eudragit. The spray-dried sample increased the solubility of felodipine 8.5-fold to 340 µg/mL. This tremendous increase in solubility is caused by the formation of a solid dispersion. In Figure 4, the SEM picture of pure felodipine and the spray-dried powder can be seen. Pure felodipine appears as cubic crystals; in the spray-dried powder, no felodipine crystals are observed.


Figure 4
In Figure 5, the dissolution profiles of the extrudate and the spray-dried powder are compared with those of pure felodipine in acidic media. Dissolution of extrudates was described in a previous study (4) and is used for comparison with the spray-dried sample. Crystalline felodipine, as expected, shows nearly no dissolution because its solubility in 0.1N hydrochlorid acid (pH 1.2) is very poor (1 mg/mL).


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
What role should the US government play in the current Ebola outbreak?
Finance development of drugs to treat/prevent disease.
Oversee medical treatment of patients in the US.
Provide treatment for patients globally.
All of the above.
No government involvement in patient treatment or drug development.
Finance development of drugs to treat/prevent disease.
29%
Oversee medical treatment of patients in the US.
10%
Provide treatment for patients globally.
6%
All of the above.
42%
No government involvement in patient treatment or drug development.
13%
Jim Miller Outsourcing Outlook Jim MillerCMO Industry Thins Out
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerFluorination Remains Key Challenge in API Synthesis
Marilyn E. Morris Guest EditorialMarilyn E. MorrisBolstering Graduate Education and Research Programs
Jill Wechsler Regulatory Watch Jill Wechsler Biopharma Manufacturers Respond to Ebola Crisis
Sean Milmo European Regulatory WatchSean MilmoHarmonizing Marketing Approval of Generic Drugs in Europe
FDA Reorganization to Promote Drug Quality
FDA Readies Quality Metrics Measures
New FDA Team to Spur Modern Drug Manufacturing
From Generics to Supergenerics
CMOs and the Track-and-Trace Race: Are You Engaged Yet?
Source: Pharmaceutical Technology,
Click here