Tracking cocrystallization of active pharmaceutical ingredients with Bbenzoic acid coformer using Broadband Acoustic resonance Dissolution Spectroscopy (BARDS)

This study investigates the use of Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS) as a detection method for the formation of cocrystals. BARDS is a novel approach that uses reproducible changes in the compressibility of a solvent as a sample dissolves to characterize and differentiate between materials and in this case cocrystallization. Two cocrystal systems with a 1:1 stoichiometry were examined, which used benzoic acid as a coformer with isonicotinamide and with theophylline. Cocrystals were prepared using dry and wet milling for periods from 1 to 40 min, and samples were analyzed using infrared spectroscopy, powder X-ray diffraction, and BARDS. Comparison of the BARDS data with the IR and PXRD data cross-validated the BARDS results. This study shows that BARDS can be used to rapidly assess the formation of these cocrystals at-line when milling or as a relatively low cost tool in preformulation product development. The data can also be used to gauge the unique entrained gas and gas volume generation of the cocrystal samples during dissolution and their dissolution kinetics

Development of low-dose protocols for thin-section CT assessment of cystic fibrosis in pediatric patients.

Purpose: To develop low-dose thin-section computed tomographic (CT) protocols for assessment of cystic fibrosis (CF) in pediatric patients and determine the clinical usefulness thereof compared with chest radiography. Materials and Methods: After institutional review board approval and informed consent from patients or guardians were obtained, 14 patients with CF and 11 patients without CF (16 male, nine female; mean age, 12.6 years ± 5.4 [standard deviation]; range, 3.5–25 years) who underwent imaging for clinical reasons underwent low-dose thin-section CT. Sections 1 mm thick (protocol A) were used in 10 patients, and sections 0.5 mm thick (protocol B) were used in 15 patients at six levels at 120 kVp and 30–50 mA. Image quality and diagnostic acceptability were scored qualitatively and quantitatively by two radiologists who also quantified disease severity at thin-section CT and chest radiography. Effective doses were calculated by using a CT dosimetry calculator. Results: Low-dose thin-section CT was performed with mean effective doses of 0.19 mSv ± 0.03 for protocol A and 0.14 mSv ± 0.04 for protocol B (P < .005). Diagnostic acceptability and depiction of bronchovascular structures at lung window settings were graded as almost excellent for both protocols, but protocol B was inferior to protocol A for mediastinal assessment (P < .02). Patients with CF had moderate lung disease with a mean Bhalla score of 9.2 ± 5.3 (range, 0–19), compared with that of patients without CF (1.1 ± 1.4; P < .001). There was excellent correlation between thin-section CT and chest radiography (r = 0.88–0.92; P < .001). Conclusion: Low-dose thin-section CT can be performed at lower effective doses than can standard CT, approaching those of chest radiography. Low-dose thin-section CT could be appropriate for evaluating bronchiectasis in pediatric patients, yielding appropriate information about lung parenchyma and bronchovascular structures

The sound of tablets during coating erosion, disintegration, deaggregation and dissolution

This research aims to address a gap in our understanding of the mechanisms by which pharmaceutical tablets achieve highly reproducible and predictable drug release. The present industrial and regulatory practice is centred around tablet dissolution, i.e. what follows disintegration, yet the vast majority of problems that are found in formulation dissolution testing can be traced back to the erratic disintegration behaviour of the medicinal product. It is only due to the distinct lack of quantitative measurement techniques for disintegration analysis that this situation arises. Current methods involve costly, and time-consuming test equipment, resulting in a need for more simple, green and efficient methods which have the potential to enable rapid development and to accelerate routine solid drug formulation dissolution and disintegration testing. In this study, we present a novel approach to track several sequential tablet dissolution processes, including coating erosion, disintegration, deaggregation and dissolution using Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS). BARDS, in combination with minimal usage of UV spectroscopy, can effectively track these processes. The data also show that a solid oral dose formulation has an intrinsic acoustic signature which is specific to the method of manufacture and excipient composition