Abstract
Recently, there has been an increasing interest in the application of nanotubular structures for drug delivery. There are several promising results with carbon nanotubes; however, in light of some toxicity issues, the search for alternative materials has come into focus. The objective of the present study was to investigate the influence of the applied solvent on the composite formation of titanate nanotubes (TNTs) with various drugs in order to improve their pharmacokinetics, such as solubility, stability, and bioavailability. Composites were formed by the dissolution of atenolol (ATN) and hydrochlorothiazide (HCT) in ethanol, methanol, 0.01 M hydrochloric acid or in ethanol, 1M sodium hydroxide, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), respectively, and then they were mixed with a suspension of TNTs under sonication for 30 min and vacuum-dried for 24 h. The structural properties of composites were characterized by SEM, TEM, FT-IR, differential scanning calorimetry (DSC), thermogravimetric (TG) analysis, and optical contact angle (OCA) measurements. Drug release was determined from the fast disintegrating tablets using a dissolution tester coupled with a UV–Vis spectrometer. The results revealed that not only the good solubility of the drug in the applied solvent, but also the high volatility of the solvent, is necessary for an optimal composite-formation process.
Highlights
Oral administration is the main route of drug administration for a systemic effect [1]
The present study aims to optimize the composite formation of titanate nanotubes (TNTs) with atenolol (ATN) and hydrochlorothiazide (HCT), improving the solubility and bioavailability of the active pharmaceutical ingredients (APIs)
The results of the contact angle measurements showed no significant difference in the surface characteristics of the new and the previous batch of TNTs (Table 2)
Summary
Oral administration is the main route of drug administration for a systemic effect [1]. Administered drugs should be released from the dosage form and dissolve before absorption Numerous attempts such as complexation, particle size reduction, solid state alternation, the application of soft gel technology, solid dispersions, using cosolvents or forming emulsions, microemulsions, micelles, polymeric micelles, liposomes, pharmaceutical salts, and pro-drugs have been made to increase the dissolution rate of the drugs in order to improve their bioavailability [2]. Many sensitive techniques can be used to detect the trace amounts of solvents, such as differential scanning calorimetry (DSC), thermogravimetric (TG) analysis, or differential thermal analysis (DTA) [2] The upsides of this method are the ability to control drug particle size by monitoring the temperature and the solvent evaporation rate [3], the capability of evaporating solvents at a lower temperature, and reduced pressure for thermolabile drugs or for frozen systems [2]. The downsides of this method are the difficulty of choosing the appropriate solvent for both the drug and the carrier, since most of the carriers are hydrophilic while the drugs are hydrophobic [12], the necessity of complete solvent removal, especially if the solvents can plasticize the carrier [13], and the large volume of solvent required to dissolve both the drug and the carrier, which is not economical in some cases [2]
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