The study aims to elucidate the transformations of anhydrous olanzapine Form I (OLZ FI) into the hydrate forms, when stored at a high relative humidity or suspended in an aqueous media, in the presence of polymers. OLZ FI and physical mixtures (3:1 and 1:1, as powders or compacts) of olanzapine with polyethylene glycol (PEG-6000), polyvinylpyrrolidone (PVP K25) and hydroxypropylcellulose (HPC-LF) were stored (75%RH/25 °C, 75%RH/40 °C and 93%RH/25 °C) for 28 days. OLZ FI and the physical mixtures were also suspended in water under stirring (200 rpm/60 min). Samples were collected at different time points and vacuum filtered. OLZ FI showed to hydrate at 75%RH/25 °C when stored in the presence of HPC and PEG. At 93%RH all polymers affected the kinetics of hydration of OLZ FI with PVP as the only polymer with the ability to minimize the formation of the hydrate. When olanzapine was suspended in water with HPC and PVP the formation of the hydrate was inhibited. Compaction of the powders before storage led to an increase of the hydrate conversion rate of olanzapine on the first week of storage, due to a partial amorphisation of olanzapine present at the tablet surface. When stored at high humidity environments OLZ FI converted into dihydrate D and, when exposed to aqueous environments in the presence of different polymers converted into dihydrates B and E. From an industrial point of view, this study highlighted the importance of the excipient's choice for OLZ formulations, so that a final OLZ medicine can have a consistent quality and performance throughout the entire medicine's shelf life.
Despite the numerous advantages of powder formulations, few studies have described their nasal drug absorption. The first aim of this study was to compare the drug absorption from powder formulation with that from a liquid formulation in rats. Since pharmaceutical excipients are usually added to most powder formulations, the second aim of the study was to investigate the effect of hydroxypropyl cellulose (HPC) on nasal drug absorption from the powder. Three types of HPC with different polymerization degrees were used: HPC(SL), HPC(M), and HPC(H). The model drugs were warfarin (BCS Class I), piroxicam (BCS Class II), and sumatriptan (BCS Class III). The absorption of these model drugs in the powder form was higher than that from the solution. All HPCs failed to enhance warfarin absorption, while the piroxicam absorption was enhanced only by HPC(M). Sumatriptan absorption was not enhanced by HPC(SL), but by HPC(M) and HPC(H). The differences in nasal absorption of the three model drugs promoted by HPCs depend on the permeability and solubility of the drug. Moreover, the nasal retention of different formulations was increased by HPCs. Because HPCs showed no toxic effect on the nasal epithelium. These findings indicate that powder formulations supplemented with HPC are a valuable and promising approach to increase the nasal absorption of highly soluble and poorly permeable drugs.
This research study aimed to develop a new strategy for using a polymer blend in solid dispersion (SD) for dissolution enhancement of poorly water-soluble drugs. SDs with different blends of hydrophilic-hydrophobic polymers (zein/hydroxypropyl methylcellulose – zein/HPMC) were prepared using spray drying to modulate the drug crystal and polymer-drug interactions in SDs. Physicochemical characterizations, including power X-ray diffraction and Fourier transform infrared spectroscopy, were performed to elucidate the roles of the blends in SDs. Although hydrophobic polymers played a key role in changing the model drug from a crystal to an amorphous state, the dissolution rate was limited due to the wetting property. Fortunately, the hydrophilic-hydrophobic blend not only reduced the drug crystallinity but also resulted in a hydrogen bonding interaction between the drugs and the polymer for a dissolution rate improvement. This work may contribute to a new generation of solid dispersion using a blend of hydrophilic-hydrophobic polymers for an effective dissolution enhancement of poorly water-solble drugs.
BIOGRUND’s one-step binding agent CompactCel® LUB combines the properties of a dry binder and lubricant. It’s a micronized and homogeneous powder compound of Hydroxypropylcellulose (HPC),oil, wax and vegetable rice extract. When tableting processes are required it is always a challenge to find the right amount of lubricant for the blended powder formulation. By using a lubricant too rarely it may cause punch filming during the compaction in the tableting machine. By using too much lubricant it could decrease the tablet hardness or increase the tablet disintegration times. These effects occur particularly when magnesium stearate is used.
The objective of the present study was to formulate and evaluate buccal patches containing combination of lisinopril (LP) and hydrochlorothiazide (HCZ). Approach: Films were fabricated by solvent casting method, using combination of mucoadhesive polymers such as hydroxypropylmethyl cellulose (HPMC), hydroxypropyl cellulose (HPC), polyvinyl alcohol (PVA) and polyvinyl pyrolidone (PVP) and ethyl cellulose (EC) as backing layer. The patches were evaluated for physicochemical characteristics such as weight, thickness, surface pH, folding endurance, bioadhesive strength, swelling index, drug content, tensile strength, elongation at break, mucoadhesion time, in vitro and ex