الفهرس 
Description
Car boxy methyl celluloseOnly 14 pages are availabe for public view
 |  | from | 133 |  |  |
| | | from | 133 | | |
Abstract
Nimodipine is a dihydropyridine calcium channel blocker with
specific selectivity to brain vasculature. It works by inducing dilatation
of the small resistance cerebral vessels and increases cerebral blood
flow in damaged regions of the brain. The main therapeutic use of
nimodipine is to prevent and treat delayed ischemia secondary to
aneurysmal subrachronoid hemorrhage. Therefore, most patients on
nimodipine are critical care unit patients.
Nimodipine has limited aqueous solubility that leads to poor
bioavailability (13%). Having short half-life, this makes it a suitable
candidate for sustained release formulation. Nimodipine is absorbed
mostly from upper gastro-intestinal tract. For such drug with short halflife
and narrow absorption window in upper gastrointestinal tract, a
gastro retentive in situ gel sustained release drug delivery systems can
overcome this problem and improves drug bioavailability.
Oral in situ gel forming liquids are newly introduced strategy
for sustaining the release of drug; they are polymeric solutions which
are in liquid form outside the body but undergo sol to gel
transformation after administration. In these studies, the mechanism of
gel formation is electrolyte triggered. Incorporation of calcium chloride
and sodium citrate in the formulation is important as it forms calcium
complex that ensures fluidity while in the bottle. Upon exposure to
stomach acidity, this complex breaks immediately liberating free
calcium ions that interacts with alginate chains resulting in spontaneous
gelation via ionic crosslinking.
Abstract X
Pharmaceutical Technology department, College of Pharmacy, University of Tanta, Tanta, Egypt.
The aim of this work was to formulate oral in situ gelling liquid
dosage form of nimodipine with potential for gastro-retention via
mucoadhesion. Before incorporation in in situ gel forming polymers,
nimodipine dissolution was improved by solid dispersion (SD)
technique using poloxamer 407 as hydrophilic matrix in three different
ratios of drug to polymer (0.5:1, 1:1, 1:2), the solid dispersions were
prepared by hot melting method after which the resultant microparticles
were further investigated by FTIR spectroscopic, X-ray diffraction and
scanning electron microscopy (SEM) techniques. The rate of
nimodipine release from the prepared SD micro-particles was
investigated with reference to the unprocessed drug as a control; the
dissolution medium was 900 ml of simulated gastric without enzymes.
The optimized SD formulation enough to produce 3mg/ml of drug was
incorporated in sodium alginate dispersions in presence or absence of
carboxy methyl cellulose. The sodium alginate dispersions of three
different concentrations (1%, 1.5%, 2%w/v giving formulations F1, F2
and F3, respectively) were prepared by using two different
concentrations of cross linker components in order to investigate the
effect of the concentration of cross linker on the release behavior of
drug from in situ gelling systems. Carboxy methyl cellulose (CMC)
was added to the optimized sodium alginate formula F1 (1% alginate,
0.075% calcium chloride and 0.25% sodium citrate w/v). Formulations
F4, F5 and F6 were obtained containing 0.5, 1 and 1.5%w/v CMC,
respectively. The latter was added to augment mucoadhesive properties
and reduce liquefaction of the gel layer, thus prolonging gastric
retention of the drug in stomach. Viscosity is determined by using
Brookfield viscometer for in situ gel forming liquids in presence and
Abstract XI
Pharmaceutical Technology department, College of Pharmacy, University of Tanta, Tanta, Egypt.
absence of CMC, in order to ensure pour ability of the gel liquids
outside body.
The in situ gel forming capacity test was performed to ensure
the ability of the liquid to transform into gel upon exposure to suitable
media that initiate gelation inside body. The bio-adhesive strength of
selected alginate dispersions was measured using rabbit intestine as a
model mucosal membrane; The adhesion force and bond strength were
calculated.
In order to study the In vitro drug release of nimodipine from in
situ gelling systems, 900 ml of simulated gastric fluids without
enzymes was used.To confirm the stomach retentive capability of the
prepared in situ gelling systems, X-ray radiography was conducted for
rabbit before and after being fed with formula F4, with lowest CMC
contents. Barium sulfate at 15% w/v concentration was used as contrast
media.
Evaluation of nimodipine solid dispersions
The FTIR spectroscopy excluded any interaction between
nimodipine and matrix forming polymer. The thermal analysis and Xray
reflected possible transformation in the crystalline structure of the
drug into more soluble amorphous form. Solid dispersion microparticles
showed a significant increase in dissolution behavior of the
drug, there was about 4-fold enhancement in Q5 of nimodipine which
was increased by increasing poloxamer 407 concentrations. Percent of
drug released after 5 min was (22%, 56% and 51%) for SD1, SD2 and
SD3 respectively, compared to Q5 equal to (5.4%) for the pure drug.
Abstract XII
Pharmaceutical Technology department, College of Pharmacy, University of Tanta, Tanta, Egypt.
Evaluation of in situ gelling systems:
For in situ forming systems, the viscosity of the formulation
depended on the concentration of sodium alginate with the viscosity
increasing with increasing alginate content. Addition of CMC increased
the viscosity of the formulation in a concentration dependent pattern
due to more chain interaction between alginate and CMC polymers. All
formulations are pourable with adequate viscosity outside the body.
Increasing alginate concentration increased the gel forming
capacity as reflected by increasing the weight of the recovered gel, For
CMC containing formulations, gel mass depended on CMC
concentration which increased at higher CMC contents this is attributed
to chain entanglement which provides higher degree of crosslinking.
The bio-adhesion strength of the prepared in situ gelling liquids
depended on the composition of each system with increasing alginate
concentration increasing the bio-adhesive properties; Addition of CMC
largely increased the bio-adhesive force.
Dissolution parameters showed a sustained release pattern with
dependence of the release rate on the concentration of sodium alginate.
The formulations F1, F2 and F3 are dispersions of increasing
concentrations of sodium alginate (1%, 1.5% and 2% w/v) respectively.
The release rate of the drug decreased with increasing alginate contents.
The effect of degree of crosslinking on drug release from in situ gelling
systems was evaluated, it can be noticed that increasing calcium ions
concentration has a substantial effect on drug dissolution behavior.
Drug release was more extended from all formulations having
duplicated concentrations of cross linkers compared to their parent
batches prepared using lower concentrations.
Abstract XIII
Pharmaceutical Technology department, College of Pharmacy, University of Tanta, Tanta, Egypt.
Evaluation of CMC containing alginate systems
Formula F1 (1% w/v alginate) was used as prototype to prepare
different systems with increasing concentration of CMC to avoid
possible massive increase in viscosity upon CMC addition that might
affect liquid pour-ability. For formulations containing CMC, a
substantial decrease in drug release was observed with release
efficiency significantly reduced. This pattern could be due to more
physical entanglement between alginate and CMC chains resulting in
formation of more firm gel. According to R2 values, drug release from
all in situ gelling systems followed Higuchi model Therefore, it can be
interpreted that the primary mechanism of drug release is diffusion
controlled release. X-ray imaging in rabbit confirmed gastro-retentive
property of the system.
The study provides the formulator with a range of gastroretentive
controlled release formulations of nimodipine while
maintaining the convenience of administration via nasogastric tubing
with potential for enhanced bioavailability.