Powder bed fusion-laser beam (PBF-LB) three-dimensional (3D) printing: Influence of laser hatching distance on the properties of zolpidem tartrate tablets.

Laser sintering, known as powder bed fusion-laser beam (PBF-LB), offers promising potential for the fabrication of patient-specific drugs. The aim of this study was to provide an insight into the PBF-LB process with regard to the process parameters, in particular the laser hatching distance, and its influence on the properties of zolpidem tartrate (ZT) tablets. PHARMACOAT® 603 was used as the polymer, while Candurin® Gold Sheen and AEROSIL® 200 were added to facilitate 3D printing. The particle size distribution of the powder blend showed that the layer height should be set to 100 µm, while the laser hatching distance was varied in five different steps (50, 100, 150, 200 and 250 µm), keeping the temperature and laser scanning speed constant. Increasing the laser hatching distance and decreasing the laser energy input led to a decrease in the colour intensity, mass, density and hardness of the ZT tablets, while the disintegration and dissolution rate were faster due to the more fragile bonds between the particles. The laser hatching distance also influenced the ZT dosage, indicating the importance of this process parameter in the production of presonalized drugs. The absence of drug-polymer interactions and the amorphization of the ZT were confirmed.

Study on a Three-Step Rapid Assembly of Zolpidem and Its Fluorinated Analogues Employing Microwave-Assisted Chemistry.

We developed an efficient microwave-assisted three-step synthesis of zolpidem and its fluorinated analogues 1-3. The procedure relays on the utilization of easily accessible and inexpensive starting materials. Our protocol shows superior performance in terms of yield and purity of products, compared to conventional heating systems. Notably, the total time needed for reaction accomplishment is significantly lower comparing to oil bath heating systems. Finally, we have performed a detailed study on the preparation of zolpidem tartrate salt I, and we assessed its particle-sizes using a polarizing microscope. Our goal was to select the appropriate method that generates the acceptable particle-size, since the solid-size directly influences solubility in biological fluids and further bioavailability. We believe that the disclosed procedure will help to produce a lab-scale quantity of zolpidem and its fluorinated derivatives 1-3, as well as zolpidem tartrate salt I, with suitable fine-particle size for further biological experimentation.

Evaluation of an activated carbon disposal system for safe disposal of model prescription sedative medications.

Lack of a safe and convenient disposal method for expired and unused medications may lead to many problems such as accidental exposure, intentional misuse, and food and water contamination. Activated carbon can offer safe disposal of medications due to its highly porous structure, which exerts strong physical adsorption forces with chemicals. This study aimed to evaluate the efficiency of an activated carbon-based drug disposal system for deactivating three model sedative prescription medications. Deactivation was performed by mixing the medication, activated carbon, and tap water. Desorption was evaluated by exposing the deactivation system to wash-out solutions. Rapid, precise, accurate, and sensitive HPLC-UV method for each drug was successfully developed, validated and employed. Results of the 28-day deactivation study showed that on average, more than 94.00% of drugs were rapidly deactivated within 8 hours. All drugs reached more than 99.00% deactivation by the end of 28-day period. Desorption study demonstrated that all medications were retained by the system, with insignificant amount of drug (0.25%) leached into the washout solutions within 24 hours. In conclusion, activated carbon rapidly and successfully deactivated the medications tested, suggesting activated carbon-based drug disposal system provides a convenient, secure, and effective method for unused medication.

Comparative bioavailability of two zolpidem hemitartrate formulations in healthy human Brazilian volunteers using high-performance liquid chromatography coupled to tandem mass spectrometry.

To assess the bioequivalence of two zolpidem hemitartrate formulations in 30 healthy volunteers. Plasma samples were obtained over a 24 h period. Plasma concentrations of zolpidem were analyzed by liquid chromatography coupled to tandem mass spectrometry with positive ion electrospray ionization using multiple reaction monitoring. Values of peak concentration (Cmax ), area under curve (AUC), half-life, elimination constant, volume of distribution and clearance showed statistically significant differences when comparing women (604.34 ng h/ml, 127.36 ng/ml, 4.4 h, 0.18 1/h, 50.56 L and 8.55 L/h, respectively) and men (276.1 ng h/ml, 70.9 ng/ml, 3.3 h, 0.26 1/h, 91.42 L and 24.34 L/h, respectively), receiving the same dose (5 mg), respectively. The geometric means with corresponding 90% confidence interval for Test/Reference percentage ratios were 99.73% (CI 93.69-106.16) for Cmax, 97.44% (90% CI = 91.85-103.37%) for area under curve of plasma concentration until the last concentration observed (AUClast ) and 98.30% (90% CI = 92.48-104.49) for the area under curve between the first sample (pre-dosage) and infinity (AUC0-inf ). Since the 90% CI for AUClast , AUC0-inf and Cmax ratios were within the 80-125% interval proposed by the US Food and Drug Administration, it was concluded that zolpidem hemitartrate formulation (5 mg orodispersible tablet) is bioequivalent to the zolpidem hemitartrate formulation (Patz SL 5 mg sublingual tablet) with regard to both the rate and the extent of absorption. A new formulation of zolpidem 2.5 mg may be useful in women for the same clinical benefits as the 5 mg formulation in men.

Evaluation of Dissolution Profile between Original and Generic Products of Zolpidem Tartrate by Microdialysis-HPLC.

The evaluation of the dissolution profile of hypnotic drugs is important to promote switching from original products to generic products by removing distrust in generic hypnotics. In this study, we investigated differences in the dissolution profiles between original and generic products (GE-D, GE-S, and GE-T) in commercially available zolpidem tartrate (ZOL) products using the HPLC method using a connected microdialysis probe (microdialysis-HPLC method). Although the degree of hardness and the disintegration time were not different among the original, GE-S, and GE-T, GE-D was 1.4 times harder than the other products. The disintegration time of GE-D was approximately twice as long as that of the original product. Generic products dissolved rapidly as compared with the original product, however, the dissolution rate in the ZOL powder (milled ZOL product) was not different between the original and generic products. Macrogol 6000 (polyethylene glycol (PEG)-6000) was used in the generic products, and this additive was the only PEG difference from the original product. We investigated whether the PEG in the product affected the solubility of ZOL and found that the addition of PEG-4000 or PEG-6000 significantly increased the dissolution rate. These results suggest that the solubility of ZOL may be increased by PEG when the product is disintegrated, resulting in the increased dissolution rate in the generic products. In conclusion, we found that the difference of PEG affected the dissolution profile in the disintegration process using the microdialysis-HPLC method. This finding can help ensure the safety of milled products and the selection of additives.