[Preparation and quality control of pyridostigmine bromide orally disintegrating tablet].

OBJECTIVE: To prepare orally disintegrating tablets containing pyridostigmine bromide and optimize formulations. METHODS: Solid dispersion was prepared using solvent evaporation-deposition method. The formulation was optimized by central composite design-response surface methodology (RSM plus CCD) with disintegration time as a reference parameter. RESULTS: The orally disintegrating tablets showed integrity and were smooth with desirable taste and feel in mouth. The disintegration time was less than 30 s. The cumulative drug dissolution was around 8.5% (around 2.5 mg which was less than bitterness threshold of pyridostigmine bromide of 3 mg) within 5 min in water while the cumulative drug dissolution was higher than 95% within 2 min in 0.1 N HCl. CONCLUSION: The orally disintegrating tablets are reasonable in formulation, feasible in technology and patient-friendly.

[Pharmacokinetics of mestinon-phospholipid complex in rats].

OBJECTIVE: To determine the pharmacokinetics characteristics of mestinon-phospholipid complex (PBPLC) in rats. METHODS: This study adopted a single-dose, randomized, open-label, two-period crossover trial design. Twelve healthy rats were randomly divided into two groups. One group was orally administered with mestinon-phospholipid complex, and the other group was orally administered with reference mestinon solution (1.5 mg/kg of mestinon). The plasma concentrations of the drugs in ophthalmic vein bloods were determined using HPLC. The pharmacokinetic parameters were calculated with the aid of DAS2.1.1 software. RESULTS: Pharmacokinetic parameters of mestinon-phospholipid complex were Tmax 2 h, Cmax 22.79 microg x min/mL and AUC(0-infinity) 7128.21 microg x min/mL, which were different from those of free mestinon--Tmax, 2 h, Cmax 6.00 microg/mL and AUC(0-infinity) 1772.36 microg x min/mL. The relative bioavailability of mestinon-phospholipid complex was 410.98% of free mestinon. CONCLUSION: The oral bioavailability of mestinon increases remarkably when administered as mestinon-phospholipid complex.

Role of a novel pyridostigmine bromide-phospholipid nanocomplex in improving oral bioavailability.

A novel pyridostigmine bromide (PB)-phospholipid nanocomplex (PBPLC) was prepared to increase the bioavailability of PB. A central composite design approach was employed for process optimization. The physicochemical properties of PBPLC were investigated by means of differential scanning calorimetry, ultraviolet spectroscopy, Fourier transformed infrared spectroscopy and the n-octano/water partition coefficient. The intestinal permeability of PBPLC was observed via a single pass intestinal perfusion in rats. After oral administration of PBPLC, the concentrations of PB at predetermined time points were determined by HPLC, and the pharmacokinetic parameters were computed by DAS 2.1.1 software. Multiple linear regression analysis for process optimization revealed that the optimal PBPLC was obtained when the values of X(1), X(2), and X(3) were 8, 40°C, and 4 mg/mL, respectively. The average particle size and zeta potential of PBPLC with the optimized formulation were 204.60 nm and -25.12 mV, respectively. Non-covalent interactions between PB and phospholipids were found in the PBPLC. The n-octanol/water partition coefficient of PBPLC was substantially increased. PBPLC had better intestinal permeability in comparison with free PB. Mean plasma drug concentration-time curves of PBPLC and free PB after oral administration were both in accordance with the two-compartment open model. The values of pharmacokinetic parameters of PBPLC and free PB were the peak time (T(max)) 2 h vs 2 h, the maximum concentration (C(max)) 22.79 µg/mL vs 6.00 µg/mL, and the value of the area under the concentration vs time curve (AUC(0-∞)) 7128.21 µg·min/mL vs 1772.36 µg·min/mL, respectively. In conclusion, compared with free PB, PBPLC remarkably improves the oral bioavailability of PB, which is likely due to its higher lipophilicity and permeability.