Abstract
We tested the solubility and dissolution of tamoxifen citrate to ascertain the optimal conditions for faster dissolution. Using the solvent evaporation method and hydrophilic carriers, we formulated tamoxifen citrate (TC) that contained solid dispersions (SDs). We increased the solubility and dissolution rate of TC with a solid dispersion system that consisted of polyethylene glycol (PEG-6000), beta-cyclodextrin (β-CD), and a combination of carriers. Physicochemical characteristics of solubility (mg/ml) were found to be 0.987±0.04 (water), 1.324±0.05 (6.8pH PBS), and 1.156±0.03 (7.4 pH PBS) for F5 formulation, percentage yield was between 98.74 ± 1.11% and 99.06 ± 0.58%, drug content was between 98.06±0.58 and 99.06±1.10, and dissolution studies binary complex showed a faster release of TC as compared to a single polymer and pure drug. Furthermore, thermal properties, physicochemical drug and polymer interaction, crystal properties, and morphology were determined using differential scanning calorimetry (DSC), infrared spectroscopy (FT-IR), X-ray differential studies, and scanning electron microscopy. We used the same proportion of carrier concentrations of the formulations to calculate the solubility of TC. Our results demonstrated that increased concentrations of β-C yielded an improved solubility of TC, which was two times higher than pure TC. The uniformity in drug content was 97.99 %. A quicker drug release occurred from the binary complex formulation as seen in the dissolution profile. FTIR demonstrated an absence in the physicochemical interaction between the drug and carriers. The drug was also found to be dispersed in the amorphous state as revealed by DSC and XRD. The drug concentration did not vary during various storage conditions. Our in vivo studies demonstrated that SD displayed significantly higher values of Cmax (p < 0.05) and AUC0-24 (p < 0.05) as compared to free TC. Furthermore, Tmax in SD was significantly lower (p < 0.05), as compared to free TC.
Highlights
Pharmaceutical drugs with poor solubility, bioavailability, permeability, and rapid metabolism and elimination comprise a large percentage of drugs in the pharmaceutical market today
Our results demonstrated a percentage coefficient of variation (CV) of 2.6% and 3.1% at the lowest drug concentration, when compared to the highest drug concentration of 0.94% and 0.79%
We examined the thermograms of the physical mixtures of Tamoxifen citrate (TC)+polyethylene glycols (PEGs) and found an endothermic peak that appeared at 146.11∘C and 63.54∘C, while the TC+β-CD endothermic peak was detected at 147.51∘C and 64.20∘C
Summary
Pharmaceutical drugs with poor solubility, bioavailability, permeability, and rapid metabolism and elimination comprise a large percentage of drugs in the pharmaceutical market today. During the preformulation stage of drug development, the physicochemical properties of pharmaceutical drugs present a continuing challenge. Large efforts have been mounted in the search for optimal techniques that can yield drugs with improved solubility and dissolution and, better drug efficacy. Solid dispersion is one such technique that is currently under investigation for use in the improvement of the solubility of active pharmaceutical ingredients (API). It is currently estimated that 40–60% of pharmaceutical compounds are more lipophilic as opposed to hydrophilic [1, 2]. Tamoxifen citrate (TC) is a perfect example of a poorly soluble compound. TC is currently indicated as an adjuvant endocrine therapy
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