Quality by Design Based Formulation Study of Meloxicam-Loaded Polymeric Micelles for Intranasal Administration.

Our study aimed to develop an "ex tempore" reconstitutable, viscosity enhancer- and preservative-free meloxicam (MEL)-loaded polymeric micelle formulation, via Quality by Design (QbD) approach, exploiting the nose-to-brain pathway, as a suitable tool in the treatment of neuroinflammation. The anti-neuroinflammatory effect of nose-to-brain NSAID polymeric micelles was not studied previously, therefore its investigation is promising. Critical product parameters, encapsulation efficiency (89.4%), Z-average (101.22 ± 2.8 nm) and polydispersity index (0.149 ± 0.7) and zeta potential (-25.2 ± 0.4 mV) met the requirements of the intranasal drug delivery system (nanoDDS) and the targeted profile liquid formulation was transformed into a solid preservative-free product by freeze-drying. The viscosity (32.5 ± 0.28 mPas) and hypotonic osmolality (240 mOsmol/L) of the reconstituted formulation provides proper and enhanced absorption and probably guarantees the administration of the liquid dosage form (nasal drop and spray). The developed formulation resulted in more than 20 times faster MEL dissolution rate and five-fold higher nasal permeability compared to starting MEL. The prediction of IVIVC confirmed the great potential for in vivo brain distribution of MEL. The nose-to-brain delivery of NSAIDs such as MEL by means of nanoDDS as polymeric micelles offers an innovative opportunity to treat neuroinflammation more effectively.

Stability and Compatibility Studies of Levothyroxine Sodium in Solid Binary Systems-Instrumental Screening.

The influence of excipients on the stability of sodium levothyroxine pentahydrate (LTSS) under ambient conditions and thermal stress was evaluated. Since LTSS is a synthetic hormone with a narrow therapeutic index, the interactions of LTSS with excipients can lead to a drastic diminution of therapeutic activity. Ten commonly used pharmaceutical excipients with different roles in solid formulations were chosen as components for binary mixtures containing LTSS, namely, starch, anhydrous lactose, D-mannitol, D-sorbitol, gelatin, calcium lactate pentahydrate, magnesium stearate, methyl 2-hydroxyethyl cellulose (Tylose), colloidal SiO2 (Aerosil) and talc. As investigational tools, universal attenuated total reflectance- Fourier transform infrared spectroscopy UATR-FTIR spectroscopy and thermal analysis were chosen and used as follows: UATR-FTIR spectra were drawn up for samples kept under ambient conditions, while thermoanalytical tools (TG/DTG/HF data) were chosen to evaluate the inducing of interactions during thermal stress. The corroboration of instrumental results led to the conclusion that LTSS is incompatible with lactose, mannitol and sorbitol, and these excipients should not be considered in the development of new generic solid formulations.

Preformulation study of hydroxytyrosol butyrate / 国际药学研究杂志

Objective: To determine the apparent oil/water(O/W)partition coefficient of hydroxytyrosol butyrate(HT-Bu), and investigate the solubility, dissolution tendency and stability of HT-Bu in different buffers, so as to provide theoretical basis for the preparation research of HT-Bu. Methods: The appearance and solubility of HT-Bu were investigated, and a high performance liquid chromatography(HPLC)method was established for the quantitative determination of HT-Bu. The solubility and O/W partition coefficient of HT-Bu in different pH buffer solutions were determined by the shakeing flask method. Results: HT-Bu was slightly yellow-colored, viscous, odorless and tasteless oily liquid. The quantitative HPLC method for the HT-Bu determination showed a good linearity within the concentration range of 5-50 μg/ml(r=0.9998). The apparent O/W partition coefficient of HT-Bu was 1.0. In the acetonitrilewater(60:40, V/V) solution, HT-Bu was stable within 12 hours at room temperature. In the different pH buffer solutions(pH 2.0-9.0), the solubility of HT-Bu increased at first and then decreased with the increase of the solution pH. HT-Bu was unstable at pH 5.5, with a large amount decomposed after kept in the solution for 6 h. HT-Bu was stable at pH 8, 0 giving a little amount decomposed after 12 h in the solution, and stable at pH 7.4 showing no significant decomposition after 12 h keeping in the solution. Conclusion: HT-Bu showed a good water solubility, which is unstable in acidic and alkaline solutions.

Preformulation study on novel antischizophrenic drug DT-195 / 国际药学研究杂志

Objective: To perform a preformulation study for the novel antischizophrenic drug DT-195, so as to provide information for its formulation development. Methods: The scanning electron microscopy, X-ray powder diffraction, and the differential scanning calorimetry were used to characterize the appearance and crystalline form of DT-195, and the solubility was tested for DT-195 in different solutions. An HPLC method was established for the preformulation determination of DT-195. The apparent oil/water(O/W) partition coefficient of DT-195 and the equilibrium solubility of the drug under different pH conditions with high and low ion concentrations were determined using the established HPLC method. Results: DT-195 was an off-white crystalline powder, slightly soluble in water, with a good linearity with the peak area within the concentration range of 10-280 μg/ml(r=0.9997)in the HPLC analysis. DT- 195 was stable under acidic conditions and easily degradable under alkaline conditions. The apparent O/W partition coefficient of DT- 195 was 0.23. The solubility of DT-195 in solution decreased with the increase in the solution pH value or ion concentration. Conclusion: The established HPLC method is reliable for the determination of DT-195 and related substances with the high sensitivity, good specificity and the good separation of DT-195 and related substances. The present results have shown that DT-195 is a poorly soluble drug, and thus the improvement of DT-195 solubility in oral preparations will enhance the bioavailability in vivo.