NEBULIZED GLYCOPYRRONIUM AND FORMOTEROL, BUDESONIDE AEROSOL AERODYNAMIC ASSESSMENT WITH VIBRATING MESH AND COMPRESSOR AIR NEBULIZER: ANDERSON CASCADE IMPACTOR STUDY

Vibrating mesh nebulizers (VMN) demonstrate improved efficiency for delivery of inhaled aerosol solutions or suspensions as compared to compressor devices. The added advantages of compactness, portability and functioning as noise-free device makes them of incremental value in Home or Ambulatory settings while managing Severe Obstructive airway disease or delivery of maintenance medications in these cases. This further circumvents the need for multiple devices thereby further improving patient compliance and convenience while delivering acute or maintenance formulations including Glycopyrronium (GLY) and Formoterol (FRM)/Budesonide(BUD) nebulizing solution formulations. To further assess the clinical role and feasibility of FRM-BUD formulation delivery kinetics  with or without GLY nebulizing solution through VMN and jet  nebulizers for In- & outpatient settings, 2 comparative in-vitro lung deposition studies were carried out utilizing Anderson Cascade impactor at 30 L/min; deposited drug concentrations in different stages were suitably collected and estimated by HPLC. Post-hoc analyses with p<0.05 was considered statistically significant for intergroup differences on FRM/BUD and GLY delivered through VMN or Compressor devices.  The calculated mean fine particle dose for FRM & BUD delivered by VMN or jet nebulizer showed no statistical difference. However the mean fine particle fraction for BUD delivered by VMN was significantly better compared to jet nebulizer than that for FRM. The Residual volume at 10 mins was significantly higher with jet nebulizer. The optimal APSD for GLY nebulizing solution admixture with FRM/BUD suspension delivered through VMN and Jet nebulizer offers a clinically relevant strategy for High risk COPD cases in Acute or Home settings

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Ondansetron.

Literature data pertaining to the physicochemical, pharmaceutical, and pharmacokinetic properties of ondansetron hydrochloride dihydrate are reviewed to arrive at a decision on whether a marketing authorization of an immediate release (IR) solid oral dosage form can be approved based on a Biopharmaceutics Classification System (BCS)-based biowaiver. Ondansetron, a 5HT3 receptor antagonist, is used at doses ranging from 4 mg to 24 mg in the management of nausea and vomiting associated with chemotherapy, radiotherapy, and postoperative treatment. It is a weak base and thus exhibits pH-dependent solubility. However, it is able to meet the criteria of "high solubility" as well as "high permeability" and can therefore be classified as a BCS class I drug. Furthermore, ondansetron hydrochloride 8 mg IR tablets (Zofran® 8 mg) and multiples thereof (16 mg = Zofran® 8 mg × 2 tablets and 24 mg = Zofran® 8 mg × 3 tablets) meet the criteria of "rapidly dissolving" in dissolution testing. Ondansetron hydrochloride has a wide therapeutic window and is well-tolerated after oral administration. Based on its favorable physicochemical properties, pharmacokinetic data and the minimal risks associated with an incorrect bioequivalence decision, the BCS-based biowaiver procedure can be recommended for ondansetron hydrochloride dihydrate IR tablets