Formulation of lyotropic liquid crystal containing mulberry stem extract: influences of formulation ingredients on the formation and the nanostructure.

OBJECTIVE: This study focused on the formulation of lamellar lyotropic liquid crystal (LLC) loaded with mulberry stem extract (MSE). METHODS: The LLC formulation tested used two oils: n-dodecane or tridecyl salicylate, a co-solvent (propylene glycol) and a single (PEG-7 glyceryl cocoate) or mixed surfactant system. The mixed surfactant was PEG-7 glyceryl cocoate/PEG-40 hydrogenated castor oil/glyceryl monooleate. The LLC formation and phase behaviour were observed by polarized optical microscopy (POM) before and after MSE loading. Nanostructure determinations on these formulations following MSE loading used small angle X-ray scattering (SAXS) at 25-40°C. RESULTS: Lamellar LLCs are formed more easily with n-dodecane than tridecyl salicylate. Propylene glycol, in the aqueous phase (1 : 1), failed to form LLC due to suboptimal critical packing parameter (CPP) value. A single or mixed surfactant system also influenced the formation of lamellar LLC according to the chemical structure of both oils and especially the surfactants used. The four lamellar LLC formulations selected for MSE loading were PEG-7 glyceryl cocoate/tridecyl salicylate/water; mixed surfactant/tridecyl salicylate/water; PEG-7 glyceryl cocoate/n-dodecane/water and mixed surfactant/n-dodecane/water, named F1, F2, F3 and F4, respectively. MSE in F1 and F3 did not affect the lamellar structure, while MSE in F2 and F4 enlarged the lamellar structure. The SAXS data confirmed that the LLC formulations obtained were lamellar and the structure persisted with MSE. CONCLUSION: These lamellar formulations should find widespread application for MSE and perhaps other similar herbal cosmetics.

Average bioequivalence of clarithromycin immediate released tablet formulations in healthy male volunteers.

The objective of this study was to assess average bioequivalence of two immediate released tablet formulations of 500-mg clarithromycin tablets in 24 healthy Thai male volunteers. In a randomized, single dose, fasting state, two-period, crossover study design with a 1-week washout period, each subject received a 500-mg clarithromycin tablet. Plasma samples were collected over a 24-hour period after oral administration and were analyzed by using a validated method using high performance liquid chromatography with electrochemical detection. Pharmacokinetic parameters were determined by using noncompartmental analysis. The time to reach the maximal concentration (tmax, h), the peak concentration (Cmax, ng/mL), and the area under the curve (AUC0-infinity, ng x h/mL) of the Reference and Test formulations were 2.0 +/- 0.8 vs. 2.2 +/- 0.9, 2793 +/- 1338 vs. 2642 +/- 1344, and 17912 +/- 7360 vs. 17660 +/- 7992, respectively. Relative bioavailability was 0.99. The 90% confidence interval of Cmax and AUC0-infinity were 82.6-112.1% and 84.7-112.0%. Bioequivalence between the Test and Reference formulation can be concluded.

Formulation and development of a patch containing tamarind fruit extract by using the blended chitosan-starch as a rate-controlling matrix.

A cosmetic patch containing tamarind fruit extract was formulated and developed by blending two types of natural polymers: chitosan with molecular weight of 100 000 and starch such as corn, potato or tapioca starch. The physicochemical characteristics, i.e. flexibility, colour, transparency, integrity, gloss, water sorption and bioadhesion property and the stability of the patch without tamarind content were investigated. Stability test was performed by keeping the prepared patches at 4 degrees C, at room temperature or at 45 degrees C for 2 weeks. The results showed that the formulations composed of chitosan:corn starch ratio of 4.5 : 0.5 (CC(4.5 : 0.5)) and chitosan:tapioca starch ratios of 4.5 : 0.5 (CT(4.5 : 0.5)) and 4.0 : 1.0 (CT(4 : 1)) provide patches with favourable physical characteristics, high water sorption, good bioadhesion ability and good stability. After the lyophilized tamarind extract in an amount corresponding to 5% of tartaric acid was incorporated into the formulations of CC(4.5 : 0.5), CT(4.5 : 0.5) and CT(4 : 1), the ability of the patches to adhere to skin was improved. However, after keeping the test patches at room temperature or at 45 degrees C for 6 weeks, their colours were intensified while their flexibilities and skin adhesion properties decreased. A 12-h in vitro permeation was investigated by studying the cumulative amount of tartaric acid permeated through the Silastic membrane (Dow-Coming, Midland, MI, USA). The CC(4.5 : 0.5) patch tended to give the highest amount of tartaric acid released. The release pattern of all the blended polymeric matrices was exhibited in two distinct phases: the rapid phase, where the flux averaged 3.61 microg min(-1) mm(-2); and the slow phase, where the flux averaged 1.89 microg min(-1) mm(-2).

Freeze-drying of tert-butyl alcohol/water cosolvent systems: effects of formulation and process variables on residual solvents.

The objective of this study was to identify significant formulation and processing variables affecting levels of tert-butyl alcohol (TBA) and isopropyl alcohol (IPA) in freeze-dried solids prepared from TBA/water cosolvent systems. The variables examined were the physical state of the solute (crystalline vs amorphous), initial TBA concentration, freezing rate, cake thickness, and the temperature and duration of secondary drying. Sucrose and glycine were used as models for noncrystallizing and crystallizing solutes, respectively. The TBA concentration above which eutectic crystallization takes place was determined by differential scanning calorimetry. Model formulations were subjected to extremes of freezing rate by either dipping in liquid nitrogen or by slowly freezing on the shelf of a freeze-dryer. Dynamics of solvent loss during secondary drying was determined by withdrawing samples as a function of time at different shelf temperatures using a thief system. On the basis of these studies, the most important determinant of residual TBA level is the physical state of the solute. Freeze-dried glycine contained very low levels of residual TBA (0.01-0.03%) regardless of freezing rate or initial TBA concentration. For freeze-dried sucrose, residual TBA levels were approximately 2 orders of magnitude higher and were significantly affected by initial TBA concentration and freezing rate. For the sucrose/TBA/water system, relatively low residual TBA levels were obtained when the initial TBA level was above the threshold concentration for eutectic crystallization of TBA, whereas samples freeze-dried from solutions containing TBA concentrations below this threshold contained significantly higher levels of TBA. Residual IPA levels increased continuously with initial concentration of TBA in the sucrose/TBA/water system. Formulations of sucrose/TBA/water which were frozen rapidly contained residual TBA levels which were approximately twice those measured in the same formulation after slow freezing and drying under the same conditions. For the sucrose/TBA/water system, the temperature and time of secondary drying had only minimal influence on residual TBA in the freeze-dried solid. At low initial TBA concentrations (2%), residual TBA increases with increased cake thickness, perhaps because of the influence of depth of fill on effective freezing rate.