Determination of drug load in porous silicon microparticles by calorimetry

Abstract

Different kind of drugs can be loaded into the porous silicon microparticles for oral dosing. In cases where the drug is in its crystalline form in the pores, the amount of the loaded drug can be determined accurately using a calorimetric method, thermoporometry. Even if the drug substance is not in crystalline form a sophisticated estimation can be given. In this work ibuprofen, antipyrine, and ranitidine have been studied. Ibuprofen and antipyrine were easily detected and quantified, but ranitidine, which does not penetrate into the PSi microparticles in its crystalline form, could only be qualitatively determined. The possibility to quantify this kind of drug substance is also discussed.

Evaluation of Mesoporous TCPSi, MCM-41, SBA-15, and TUD-1 Materials as API Carriers for Oral Drug Delivery

“…The XRD patterns were in good agreement with reference data of the corresponding materials (Beck et al 1992;Hamdy et al 2005;Salonen et al 2005b;Zhao et al 1998). The XRD patterns for MCM-41 and SBA-15 materials exhibited narrow and clearly resolved hkl(100) reflections at 0.9…”

“…In reality the total drug concentration of a loaded mesoporous sample consists of the drug in the mesopores as well as possible drug content on the particle surfaces and even residue-free bulk drug from the loading solution. The detection of crystalline ibuprofen in a loaded-mesoporous solid is associated with a particle surface adsorbed drug portion in the sample (Charnay et al 2004;Lehto et al 2005;Salonen et al 2005a;Salonen et al 2005b). This was illustrated by the results of the present sample characterizations, where all the samples loaded with the high concentration solution exhibited a crystalline drug phase, i.e., portion of drug loaded on the host particle surfaces.…”

“…The HPLC and TG results of the total ibuprofen loads were in good correlation. After the total API content of a sample was determined (mean value of the HPLC and TG results used), the surface loaded portion of the total amount was quantified using DSC, according to the procedure introduced in previous studies (Lehto et al 2005;Salonen et al 2005a;Salonen et al 2005b). According to the procedure, the enthalpy of the melting endotherm of ibuprofen was used to calculate the amount of drug on the mesoporous silica/silicon particle surfaces.…”

“…We recently have introduced a method based on differential scanning calorimetry, whereby the drug component residing on the drug host particle surfaces can be readily distinguished and quantified. In combination with, for example, thermal gravimetry and/or liquid chromatography data of the total API content, a reliable quantification of the true mesopore drug loads of samples is achieved (Lehto et al 2005;Salonen et al 2005a;Salonen et al 2005b).…”

Association of a Weakly Acidic Anti-Inflammatory Drug (Ibuprofen) with a Poly(Amidoamine) Dendrimer as Studied by Molecular Dynamics Simulations

“…[40][41][42][43] To verify the suitability of the AMBER forcefield for the description of the ibuprofen molecules, we have checked characteristic properties such as the density, the Hansen solubility parameter 44 and the average dipole moment of the drug and compared it to available literature data. Namely, after the NPT MD runs, the density was stabilized at F ) 0.99 ( 0.02 g/cm 3 which compares favorably to a value of 1.06 g/cm 3 , as can be estimated for the amorphous state of ibuprofen, 45,46 whereas calculation of the total Hansen solubility parameter δ based on the cohesive energy density (see, e.g., ref 47 for a more detailed description of the procedure) rendered a value of 9.57 ( 0.46 (cal/cm 3 ) 0.5 , which is within the range of 9.39 to 9.66 (cal/cm 3 ) 0.5 reported for bulk ibuprofen. 48,49 Calculation of the average dipole moment of ibuprofen yielded a value of 1.80 ( 0.02D, which lies within the limits estimated for the more stable ibuprofen conformers.…”