Hydranal titration solvent

Atomoxetine HCl was kindly provided by Multi-APEX for Pharmaceutical Industries (Cairo, Egypt), Risperidone was kindly acquired from Delta Pharma (Cairo, Egypt), polyvinyl alcohol (Grade: High Viscosity, M.Wt: 200,000 Da) and glycine were purchased from ADVENT (Navi-Mumbai, India), stearic acid was purchased from PIOCHEM (6 October City, Giza Governorate, Egypt), compritol^® 888 ATO was kindly provided by Gattefossé Co. (Chemin de Genas St Priest, France), span 60, Hydranal^® titration solvent, pluronic F127 and HPMC K100 were purchased from Sigma-Aldrich Co. (St. Louis, MO, USA), NOVEON^® AA-1 was purchased from Lubrizol Advanced Materials Europe BVBA (Chaussee de wavre, Brussels, Belgium), potassium dihydrogen phosphate, disodium hydrogen phosphate, ammonium acetate, formic acid, methanol and acetonitrile (HPLC grade) were purchased from Merk Co. (North Wales, PA, USA).

By using Karl Fischer titration, the residual water content of the nasal inserts was determined after lyophilization process. A known volume of dry methanol (Sigma-Aldrich, Bornem, Belgium) was used to reconstitute the lyophilized insert and was left to equilibrate for 15 min. Next, a known volume of this solution was removed from the vial via a syringe, injected in the titration vessel of a Mettler Toledo V30 volumetric Karl Fischer titrator (Schwerzenbach, Switzerland), and titrated with Hydranal^® titration solvent (Sigma-Aldrich, Bornem, Belgium). The moisture content of the dry methanol was determined to subtract from the result before testing the lyophilized insert sample [44 (link),66 (link)].

Before their reconstitution, the lyophilized EVs
were characterized in terms of cake appearance and residual moisture
(RM).
The cake’s appearance is the most subjectable critical
quality attribute of lyophilized products and is evaluated by visual
inspection. Ideally, the cake should preserve the same shape and size
as the frozen product, with uniform color and texture. Despite such
expectations, there are no systematically defined criteria to accept
or reject a cake with variations that deviate from the misunderstood
term “elegant”. Acceptable and unacceptable cake appearances
are determined based on historical precedent. Many terminologies were
coined to describe variations in the cake appearance deviating from
the definition of “uniform and elegant”, i.e., collapsed
cakes, that resulted in a reduced specific surface area, melted-back
cakes, shrinkage, etc.^{44 (link)}The residual
moisture of the lyophilized samples was investigated
by the Karl Fischer titration (Karl Fischer Moisture Meter CA-31,
Mitsubishi, Japan). The hydranal titration solvent (Sigma-Aldrich,
Milano, Italy) was used to reconstitute most of the formulations to
be analyzed. In contrast, formamide was added to those samples containing
dextran, glycine, and mannitol, as they are scarcely soluble in methanol.
A titration blank was carried out in triplicate to determine the moisture
concentration in the water standard and formamide.