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AAPS PharmSciTech ( # 2013)DOI: 10.1208/s12249-013-9989-2 Polydimethylsiloxane–Indomethacin Blends and Nanoparticles Received 12 February 2013; accepted 28 May 2013 Abstract. A series of blends of polydimethylsiloxane (PDMS) and indomethacin (IMC), containing 20–80 wt.% IMC were obtained and characterized by differential scanning calorimetry, Fourier transform–infraredspectroscopy, and powder X-ray diffraction in order to observe the mutual influence of the two components.
The main thermal transitions of PDMS remained un-changed. Both the solvent (tetrahydrofuran, THF) andthe PDMS influenced the crystalline form of IMC. The blends were subsequently re-dissolved in THF, with orwithout cross-linking reagents added and precipitated into diluted aqueous solutions of siloxane-based surfac-tants. The resulted nanoparticles were analyzed by dynamic light scattering and scanning electron microscopy.
Most of the particles had diameters between 200 and 300 nm. The surfactants, the IMC content and the cross-linking influenced the particles size and polydispersity, as well as the nanoparticle yield. The maximum drugrelease from selected aqueous formulations was 30%.
KEY WORDS: indomethacin; nanoparticles; polydimethylsiloxane.
The anti-inflammatory non-steroidal drugs (AINS) are used in rheumatoid and osteoarthritis and in local inflammation (11).
Polysiloxanes have many biomedical uses, especially in The oral therapy with AINS is very efficient, but the clinical use is implantology, transdermic applications and drug delivery (1–3).
often limited due to potential side effects, like irritations and They are well-known for their biocompatibility (especially refer- ulcerations of the gastro-intestinal mucous membrane (12). These ring to high molecular weight homologs) and at the same time, well-known side effects of AINS oral administration acceler- they are among the most tested materials concerning safety ated the development of alternative pharmaceutical formula- (2,4,5). Apart the biological inertness, polysiloxanes are charac- tions, such as creams, gels, and topic foams, which allow the terized by hydrophobicity, permeability to diffusion of different local adsorption to the inflammation site, without adverse sys- substances, including gases, water vapors and drugs, as well as by temic reactions (13). Nevertheless, effective drug encapsulationfor oral or parenteral use is very important for limiting side specific visco-elastic properties (2). The controlled release of effects and maintaining efficiency. Indomethacin (IMC) is a active drugs with polydimethylsiloxane (PDMS) goes back to hydrophobic, model AINS drug in many investigations.
the 1960s (6). At the present, there are numerous commercially Different applications have been proposed for drug-load- available products in which silicones are used as actives or ex- ed nanoparticles, like targeted drug delivery, controlled re- cipients. For example, silicones act as antifoams in gastro- lease, increasing bioavailability of poor water-soluble drugs enterology, being very effective in anti-acid formulations (6).
(14,15). The nanoparticles used for this purpose, roughly having The drug release from silicone-containing formulations is dimensions between 10 and 1,000 nm, may be nanocapsules or controlled by its diffusion through the silicone network (6,7).
nanospheres. Several characteristics of the particles were recog- In our previous work, we tested the possibility of using nized as key parameters for magnified efficacy of nanoparticles PDMS as a core polymer in nanoparticles obtained by precipi- for therapeutic applications: particle size, particle shape, surface tation in the presence of different stabilizers, having a siloxane- characteristics and release of therapeutics (16).
organic structure (8–10). We have shown that cross-linking of By combining IMC and PDMS, improved results might be PDMS may occur in the nanoparticles (9,10), and that improved obtained in topical applications (due to the substantivity of stability of the particles is obtained after this step. Taking into PDMS) or oral administration (due to the low density and account the properties of polysiloxanes, in particular of PDMS, antifoam properties of PDMS). These potential benefits they can be considered an interesting alternative as polymer prompted a basic investigation on the mutual influence of the matrix for nanoparticles encapsulating drugs or other active drug and the matrix, in order to better understand processes like principles, for oral or topical formulations.
blending, encapsulation or release. In this study, the approach was to mix PDMS and IMC in different proportions in a common “Petru Poni” Institute of Macromolecular Chemistry, Aleea Gr.
organic solvent. The obtained blends were investigated by DSC, Ghica Voda 41A, 700487 Iasi, Romania.
FT-IR, and powder X-ray diffraction and their properties are Department of Natural and Synthetic Polymers, “Gh. Asachi” Technical considered the model for nanoparticles obtained thereof. The 3 To whom correspondence should be addressed. (e-mail: nanoparticles were prepared by re-dissolving the blends in THF and precipitation in water in the presence of siloxane-based 1530-9932/13/0000-0001/0 # 2013 American Association of Pharmaceutical Scientists
  • Polydimethylsiloxane–Indomethacin Blends and Nanoparticles
  • Investigation of PDMS–IMC Blends
  • Nanoparticles from PDMS–IMC Blends
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