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1.
The crystallo-co-agglomeration technique was used to design directly compressible and deformable agglomerates of talc containing
the low-dose drug bromhexine hydrochloride (BXH). The process of agglomeration involved the use of dichloromethane as a good
solvent and bridging liquid for BXH, water as a poor solvent, talc as diluent, and Tween 80 to aid dispersion of BXH and diluent
into the poor solvent. Hydroxypropyl methylcellulose (50 cps) 4% wt/wt was used to impart the desired mechanical strength
and polyethylene glycol 6000 5% wt/wt was used to impart the desired sphericity to the agglomerates. Clarity of the supernatant
was considered an endpoint for completion of the agglomeration process. The drug-to-talc ratio in optimized batch 1 (BT1)
and batch 2 (BT2) was kept at 1:15.66 and 1:24, respectively. The spherical agglomerates obtained were evaluated for topographic,
micromeritic, mechanical, deformation, compressional, and drug release properties. The agglomeration yield and drug entrapment
for both batches were above 94% wt/wt. Crushing strength and friability studies showed good handling qualities of agglomerates.
Heckel plot studies showed low mean yield pressure and high tensile strength, indicating excellent compressibility and compactibility
of agglomerates. Diametral and axial fracture of compacts showed deformation of agglomerates revealing formation of a heterogeneous
compact. Drug release was sustained for 9 hours and 5 hours from BT1 and BT2, respectively, in 0.1N HCl. Hence, the crystallo-co-agglomeration
technique can be successfully used for obtaining spherical, deformable, and directly compressible agglomerates, generating
a heterogeneous matrix system and providing sustained drug release.
Published: July 27, 2007 相似文献
2.
The purpose of this research work was to obtain directly compressible agglomerates of ibuprofen with talc by a novel crystallo-co-agglomeration
(CCA) technique, which is an extension of spherical crystallization. Ibuprofen-talc agglomerates were prepared using dichloromethane
(DCM)-water as the crystallization system. DCM acted as a good solvent for ibuprofen as well as a bridging liquid for agglomeration
of crystallized drug with talc. The agglomerates were characterized by differential scanning calorimetry, powder X-ray diffraction,
and scanning electron microscopy and were evaluated for tableting properties and for drug release. The process yielded spherical
agglomerates containing ∼95% to 96% wt/wt of ibuprofen. Agglomerates containing talc showed uniform distribution of hydroxypropylmethylcellulose
and decreased crystallinity, and deformed under pressure. The miniscular form of ibuprofen and the hydrophobicity of talc
governed the drug release rate. The batch containing a higher proportion of talc showed zeroorder kinetics and drug release
was extended up to 13 hours. The CCA technique developed in this study is suitable for obtaining agglomerates of drug with
talc as an excipient. 相似文献
3.
The purpose of this research was to obtain directly compressible agglomerates of ibuprofen-paracetamol containing a desired
ratio of drugs using a crystallo-co-agglomeration technique. Crystallo-co-agglomeration is an extension of the spherical crystallization
technique, which enables simultaneous crystallization and agglomeration of 2 or more drugs or crystallization of a drug and
its simultaneous agglomeration with another drug or excipient. Dichloromethane (DCM)-water system containing polyethylene
glycol (PEG) 6000, polyvinyl pyrollidone, and ethylcellulose was used as the crystallization system. DCM acted as a good solvent
for ibuprofen and bridging liquid for agglomeration. The process was performed at pH 5, considering the low solubility of
ibuprofen and the stability of paracetamol. Loss of paracetamol was reduced by maintaining a low process temperature and by
the addition of dextrose as a solubility suppressant. The agglomerates were characterized by differential scanning calorimetry,
powder x-ray diffraction (PXRD), and scanning electron microscopy and were evaluated for tableting properties. The spherical
agglomerates contained an ibuprofen-paracetamol ratio in the range of 1.23 to 1.36. Micromeritic, mechanical, and compressional
properties of the agglomerates were affected by incorporated polymer. The PXRD data showed reduction in intensities owing
to dilution and reduced crystallinity. Thermal data showed interaction between components at higher temperature. Ethylcellulose
imparted mechanical strength to the agglomerates as well as compacts. The agglomerates containing PEG have better comparessibility
but drug release in the initial stages was affected owing to asperity melting, yielding harder compacts. The agglomeration
and properties of agglomerates were influenced by the nature of polymer. 相似文献
4.
Renata P. Raffin Paolo Colombo Fabio Sonvico Alessandra Rossi Denise S. Jornada Adriana R. Pohlmann Silvia S. Guterres 《AAPS PharmSciTech》2009,10(2):335-345
Pantoprazole-loaded microparticles were prepared using a blend of Eudragit® S100 and Methocel® F4M. The accelerated stability was carried out during 6 months at 40°C and 75% relative humidity. In order to improve technological characteristics of the pantoprazole-loaded microparticles, soft agglomerates were prepared viewing an oral delayed release and gastro-resistant solid dosage form. The agglomeration was performed by mixing the pantoprazole microparticles with spray-dried mannitol/lecithin powders. The effects of factors such as the amount of lecithin in the spray-dried mannitol/lecithin powders and the ratio between pantoprazole microparticles and spray-dried mannitol/lecithin powders were evaluated. The pantoprazole-loaded microparticles present no significant degradation in 6 months. The agglomerates presented spherical shape, with smooth surface and very small quantity of non-agglomerated particles. The agglomerates presented different yields (35.5–79.0%), drug loading (58–101%), and mechanical properties (tensile strength varied from 44 to 69 mN mm−2), when the spray-dried mannitol/lecithin powders with different lecithin amounts were used. The biopharmaceutical characteristics of pantoprazole microparticles, i.e., their delayed-release properties, were not affected by the agglomeration process. The gastro-resistance of the agglomerates was affected by the amount of spray-dried mannitol/lecithin powders. The ratio of lecithin in the spray-dried mannitol/lecithin powders was the key factor in the agglomerate formation and in the drug release profiles. The agglomerates presenting better mechanical and biopharmaceutical characteristics were prepared with 1:2 (w/w) ratio of pantoprazole-loaded microparticles and mannitol/lecithin (80:20) powder.Key words: agglomerates, delayed release, gastro-resistance, microparticles 相似文献
5.
The purpose of this research was to obtain directly compressible agglomerates of naproxen containing disintegrant by spherical
crystallization technique. Acetone–water containing hydroxypropyl celloluse (HPC) and disintegrant was used as the crystallization
system. In this study croscarmellose sodium (Ac–Di–Sol) was employed as disintegrant. The agglomerates were characterized
by differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD), and scanning electron microscopy and were evaluated
for flow, packing and tableting properties and drug release. The growth of particle size and the spherical form of the agglomerates
resulted in formation of products with good flow and packing properties. The improved compaction properties of the agglomerated
crystals were due to their fragmentation occurred during compression. DSC and XRPD studies showed that naproxen particles,
crystallized in the presence of HPC and Ac–Di–Sol did not undergo structural modifications. The dissolution rate of naproxen
from tablets made of naproxen–(Ac–Di–Sol) agglomerates was enhanced significantly because of including the disintegrant in
to the particles. This was attributed to an increase in the surface area of the practically water insoluble drug is exposed
to the dissolution medium. In conclusion the spherical crystallization technique developed in this study is suitable for obtaining
agglomerates of drug with disintegrant. 相似文献
6.
Amelt solidification technique has been developed to obtain sustained-release waxy beads of flurbiprofen. Low glass transition
temperature (t
g) and shear-induced crystallization of flurbiprofen made it a suitable candidate for melt solidification technique. The process
involved emulsification and solidification of flurbiprofen-cetyl alcohol melt at significantly low temperature (5°C). The
effect of variables, namely, the amount of cetyl alcohol and the speed of agitation, was studied using 32 factorial design. The technique and the beads were evaluated on the basis of process and desired yield, surface topography,
Fourier-transform infrared (FT-IR), differential scanning calorimetry (DSC), particle size distribution, crushing strength,
and drug release. Average values for process and desired yields were 97% wt/wt and 26% wt/wt, respectively. No interaction
was observed between drug and excipient. Multiple regression analysis was carried out, and response surfaces were obtained.
A curvilinear relationship was observed between percentage of desired yield and the amount of cetyl alcohol. Linear decrease
in crushing strength was observed with increase in the amount of cetyl alcohol. Drug released from the beads followed zero
order kinetics. Burst release was shown to a greater extent in beads containing a lower amount of cetyl alcohol. Response
surfaces of time required for certain percentage of drug (t
D%) showed that after critical concentration of about 20% of cetyl alcohol (400 mg/batch), no significant release retardant
effect was observed. 相似文献
7.
The aim of this study was to investigate the effect of Eudragit RS 30D, talc, and verapamil hydrochloride on dissolution and mechanical properties of beads coated with "drug-layered matrices". This was accomplished with the aid of a three-factor multiple-level factorial design using percent drug release in 1 and 2 h, T(50), tensile strength, brittleness, stiffness and toughness as the responses. Beads were coated in a fluidized-bed coating unit. Surface morphology and mechanical properties were evaluated by surface profilometry and texture analysis, respectively. No cracks, flaws and fissures were observed on the surfaces. The mechanical properties were dependent on the talc/polymer ratio. The release of verapamil from the beads was influenced by matrix components. Increasing the level of both talc and Eudragit decreased the percent drug released from 67% to 4.8% and from 80.7% to 6.7% in 1 and 2 h, respectively, and increased T(50) from 0.8 to 25.7 h. It was concluded that beads could be efficiently coated with "drug-layered matrices". The release of drug, however, depends on a balance between the levels of drug, talc, and polymer, whereby desired dissolution and mechanical properties could be controlled by the talc/polymer ratio and the level of drug loading. 相似文献
8.
Kristensen J 《AAPS PharmSciTech》2006,7(4):E46-E53
The purpose of this research was to investigate the use of polyethylene glycol (PEG) solutions as the primary binder liquid
in a 2-step agglomeration process performed in a rotary processor and characterize the resulting granules and their tableting
characteristics. This was done by granulation of binary mixtures of microcrystalline cellulose (MCC) and either lactose, calcium
phosphate, acetaminophen, or theophylline, in a 1∶3 ratio, using a 50% (wt/wt) aqueous solution of PEG and water as the binder
liquid. Formulations containing lactose were agglomerated using 5 different amounts of the PEG binder solution, giving rise
to a PEG content in the range of 6% to 43% (wt/wt). The process outcome was characterized according to adhesion, yield, and
water requirement, and the prepared granules were characterized according to size, size distribution, and flow properties
as well as tableting properties. The agglomeration of all mixtures resulted in high yields of free-flowing agglomerates and
gave rise to good reproducibility of the investigated agglomerate characteristics. The process allowed for the incorporation
of 42.5% (wt/wt) PEG, which is higher than the percentage of PEG reported for other equipment. Tables of sufficient strength
could be prepared with all investigated excipients using 20% wt/wt PEG; higher PEG contents gave rise to adhesion and prolonged
disintegration. In conclusion, agglomeration in a torque-controlled rotary processor using solutions of PEG as the primary
binder liquid was found to be a robust process, suitable for the incorporation of high contents of PEG and/or drug compounds. 相似文献
9.
In this study, the use of biodegradable polymers for microencapsulation of naltrexone using solvent evaporation technique
is investigated. The use of naltrexone microspheres for the preparation of matrix devices is also studied. For this purpose,
poly(L-lactide) (PLA) microspheres containing naltrexone prepared by solvent evaporation technique were compressed at temperatures
above the Tg of the polymer. The effect of different process parameters, such as drug/polymer ratio and stirring rate during
preparation of microspheres, on the morphology, size distribution, and in vitro drug release of microspheres was studied.
As expected, stirring rate influenced particle size distribution of microspheres and hence drug release profiles. By increasing
the stirring speed from 400 to 1200 rpm, the mean diameter of microspheres decreased from 251 μm to 104 μm. The drug release
rate from smaller microspheres was faster than from larger microspheres. However, drug release from microspheres with low
drug content (20% wt/wt) was not affected by the particle size of microspheres. Increasing the drug content of microspheres
from 20% to 50% wt/wt led to significantly faster drug release from microspheres. It was also shown that drug release from
matrix devices prepared by compression of naltrexone microspheres is much slower than that of microspheres. No burst release
was observed with matrix devices. Applying higher compression force, when compressing microspheres to produce tablets, resulted
in lower drug release from matrix devices. The results suggest that by regulating different variables, desired release profiles
of naltrexone can be achieved using a PLA microparticulate system or matrix devices. 相似文献
10.
The purpose of this research was to mask the intensely bitter taste of ondansetron HCl and to formulate a rapiddisintegrating
tablet (RDT) of the taste-maske drug. Taste masking was done by complexing ondansetron HCl with aminoalkyl methacrylate copolymer
(Eudragit EPO) in different ratios by the precipitation method. Drug-polymer complexes (DPCs) were tested for drug content,
in vitro taste in simulated salivary fluid (SSF) of pH 6.2, and molecular property. Complex that did not release drug in SSF
was considered taste-masked and selected for formulation RDTs. The complex with drug-polymer ratio of 8∶2 did not show drug
release in SSF; therefore, it was selected. The properties of tablets such as tensile strength, wetting time, water absorption
ratio, in vitro disintegration time, and disintegration in the oral cavity were investigated to elucidate the wetting and
disintegration characteristics of tablets. Polyplasdone XL-10 7% wt/wt gave the minimum disintegration time. Tablets of batch
F4 containing spray-dried mannitol and microcrystalline cellulose in the ratio 1∶1 and 7% wt/wt Polyplasdone XL-10 showed
faster disintegration, within 12.5 seconds, than the marketed tablet (112 seconds). Good correlation between in vitro disintegration
behavior and in the oral cavity was recognized. Taste evaluation of RDT in human volunteers revealed considerable taste masking
with the degree of bitterness below threshold value (0.5) ultimately reaching to 0 within 15 minutes, whereas ondansetron
HCl was rated intensely bitter with a score of 3 for 10 minutes. Tablets of batch F4 also revealed rapid drug release (t90, 60 seconds) in SGF compared with marketed formulation (t90, 240 seconds;P<.01). Thus, results conclusively demonstrated successful masking of taste and rapid disintegration of the formulated tablets
in the oral cavity.
Published: June 22, 2007 相似文献
11.
The purpose of this research was to formulate tasteless complexes of ciprofloxacin with Indion 234 and to evaluate molecular
properties of drug complexes. The effect of batch and column process, complexation time, temperature, and pH on ciprofloxacin
loading on Indion 234 is reported. Drug resin complexes (DRC) were characterized by infrared spectroscopy, thermal analysis,
and x-ray diffraction pattern. Ciprofloxacin release from DRC is obtained at salivary and gastric pH and in the presence of
electrolytes. The efficient drug loading was evident in batch process using activated Indion 234 with a drug-resin ratio of
1∶1.3. Drug complexation enhanced with pH from 1.2 to 6, while temperature did not affect the complexation process. Infrared
spectroscopy revealed complexation of—NH (drug) with Indion 234. DRC are amorphous in nature. Drug release from DRC in salivary
pH was insufficient to impart bitter taste. Volunteers rated the complex as tasteless and agreeable. Complete drug release
was observed at gastric pH in 2 hours. The drug release was accelerated in the presence of electrolytes. Indion 234 is inexpensive,
and the simple technique is effective for bitterness masking of ciprofloxacin. 相似文献
12.
The aims of the study were to evaluate the effect of high shear mixer (HSM) granulation process parameters and scale-up on wet mass consistency and granulation characteristics. A mixer torque rheometer (MTR) was employed to evaluate the granulating solvents used (water, isopropanol, and 1:1 vol/vol mixture of both) based on the wet mass consistency. Gral 25 and mini-HSM were used for the granulation. The MTR study showed that the water significantly enhanced the beta-cyclodextrin (beta CD) binding tendency and the strength of liquid bridges formed between the particles, whereas the isopropanol/water mixture yielded more suitable agglomerates. Mini-HSM granulation with the isopropanol/water mixture (1:1 vol/vol) showed a reduction in the extent of torque value rise by increasing the impeller speed as a result of more breakdown of agglomerates than coalescence. In contrast, increasing the impeller speed of the Gral 25 resulted in higher torque readings, larger granule size, and consequently, slower dissolution. This was due to a remarkable rise in temperature during Gral granulation that reduced the isopropanol/water ratio in the granulating solvent as a result of evaporation and consequently increased the beta CD binding strength. In general, the HSM granulation retarded ibuprofen dissolution compared with the physical mixture because of densification and agglomeration. However, a successful HSM granulation scale-up was not achieved due to the difference in the solvent mixture's effect from 1 scale to the other. 相似文献
13.
M. Maghsoodi 《AAPS PharmSciTech》2009,10(1):120-128
Microparticles of naproxen with Eudragit L100 and Aerosil were prepared by the emulsion solvent diffusion method in order
to avoid local gastrointestinal irritation, one of the major side effects of nonsteroidal anti-inflammatory drugs after oral
ingestion. The process of preparation involved the use of ethanol as good solvent, dichloromethane as a bridging liquid, water
as poor solvent, Aerosil as anti-adhesion agent, and sodium dodecyl sulfate to aid in the dispersion of the drug and excipients
into the poor solvent. The obtained microparticles were evaluated for micromeritic properties, yield, encapsulation efficiency,
drug physical state, and drug release properties. The influence of formulation factors and preparation condition (polymer/naproxen
ratio, Aerosil/polymer ratio, and the initial difference of temperature between the solvent and nonsolvent) on the properties
of the microparticles were also examined. The resultant microparticles were finely spherical and uniform with high incorporation
efficiency (>79%) and yield (>71%). The incorporation efficiency was enhanced with increasing the ratio of excipients to drug
and the initial difference of temperature between the solvent and nonsolvent. The mean diameter of the microparticles was
influenced by all of the manufacturing parameters. Studies carried out to characterize the micromeritic properties of formulations,
such as flowability and packability, showed that microparticles were suitable for further pharmaceutical manipulation (e.g.,
capsule filling). Drug release studies of the microparticles confirmed the gastroresistance, and mathematical studies showed
that the drug released followed a Hixon and Crowell kinetic. These microparticles represent a simple method for the preparation
of drug-loaded enteric microparticles with desired micromeritic properties and gastroresistance release. 相似文献
14.
The aims of the study were to evaluate the effect of high shear mixer (HSM) granulation process parameters and scale-up on wet mass consistency and granulation characteristics. A mixer torque rheometer (MTR) was employed to evaluate the granulating solvents used (water, isopropanol, and 1:1 vol/vol mixture of both) based on the wet mass consistency. Gral 25 and mini-HSM were used for the granulation. The MTR study showed that the water significantly enhanced the beta-cyclodextrin (βCD) binding tendency and the strength of liquid bridges formed between the particles, whereas the isopropanol/water mixture yielded more suitable agglomerates. Mini-HSM granulation with the isopropanol/water mixture (1:1 vol/vol) showed a reduction in the extent of torque value rise by increasing the impeller speed as a result of more breakdown of agglomerates than coalescence. In contrast, increasing the impeller speed of the Gral 25 resulted in higher torque readings, larger granule size, and consequently, slower dissolution. This was due to a remarkable rise in temperature during Gral granulation that reduced the isopropanol/water ratio in the granulating solvent as a result of evaporation and consequently increased the βCD binding strength. In general, the HSM granulation retarded ibuprofen dissolution compared with the physical mixture because of densification and agglomeration. However, a successful HSM granulation scale-up was not achieved due to the difference in the solvent mixture’s effect from 1 scale to the other. 相似文献
15.
The present research studied the effect of sintering technique in the development of a controlled release formulation for ketorolac tromethamine. The method consisted of mixing drug and wax powder (Compritol® 888 ATO) along with lactose as diluent and talc as lubricant followed by direct compression at room temperature. The compressed fluffy matrices were kept at 80°C for 1, 2, and 3 h for sintering. The sintered tablets were characterized by their physical parameters and in vitro dissolution profile. The sintering time markedly affected the drug release properties of Compritol® 888 ATO matrices. It is notable that the release rate of ketorolac tromethamine from matrices was inversely related to the time of sintering. This may be due to the increase in the extent and firmness of sintering which further compacts the mass so that drug release is affected. Contact angle measurement and scanning electron microscopy analysis indicated that heat treatment caused the wax to melt and redistribute. This redistributed wax formed a network-like structure in which the drug along with lactose is entrapped. This particular formed matrix is responsible for retarding the drug release. Fourier transform infrared spectroscopy results did not show any drug–wax interaction due to sintering. Differential scanning calorimetric and powder X-ray diffraction studies ruled out the occurrence of solid solution and polymorphic changes of the drug. Drug release from the wax tablets with or without sintering was best described by the Higuchi equation. 相似文献
16.
The aim of this study was to formulate a self-emulsifying system (SES) containing a lipophilic drug, loratadine, and to explore
the potential of preformed porous polystyrene beads (PPB) to act as carriers for such SES. Isotropic SES was formulated, which
comprised Captex 200 (63% wt/wt), Cremophore EL (16% wt/wt), Capmul MCM (16% wt/wt), and loratadine (5% wt/wt). SES was evaluated
for droplet size, drug content, and in vitro drug release. SES was loaded into preformed and characterized PPB using solvent
evaporation method. SES-loaded PPB were evaluated using scanning electron microscopy (SEM) for density, specific surface area
(SBET), loading efficiency, drug content, and in vitro drug release. After SES loading, specific surface area reduced drastically,
indicating filling of PPB micropores with SES. Loading efficiency was least for small size (SS) and comparable for medium
size (MS) and large size (LS) PPB fractions. In vitro drug release was rapid in case of SS beads due to the presence of SES
near to surface. LS fraction showed inadequate drug release owing to presence of deeper micropores that resisted outward diffusion
of entrapped SES. Leaching of SES from micropores was the rate-limiting step for drug release. Geometrical features such as
bead size and pore architecture of PPB were found to govern the loading efficiency and in vitro drug release from SES-loaded
PPB.
Published: March 24, 2006 相似文献
17.
The purpose of this research was to study the influence of type of chitosan with different molecular weights, ie, 190 and
419 kDa, on properties of pellets prepared by extrusion/ spheronization. The formulations, consisting of acetaminophen as
model drug, chitosan, microcrystalline cellulose (MCC), and dibasic calcium phosphate dihydrate with/without sodium alginate,
were extruded using a twin-screw extruder and water as the granulating liquid. With 30% wt/wt MCC and no added sodium alginate,
spherical pellets were produced containing low and high molecular weight chitosan at a maximum amount of 60% and 40% wt/wt,
respectively. With sodium alginate (2.5% wt/wt), pellets with either type of chitosan (60% wt/wt), MCC (17.5% wt/wt), and
acetaminophen (20% wt/wt) could be produced indicating an improved pelletforming ability. Type and amount of chitosan and
added sodium alginate affected physical properties of pellets including size, roundness, crushing force, and drug release.
Low molecular weight chitosan produced pellets with higher mean diameter, sphericity, and crushing force. Additionally, the
pellets made of low molecular weight chitosan and added sodium alginate showed faster drug release in 0.1 N HCl but had slower
drug release in pH 7.4 phosphate buffer. This indicated that drug release from pellets could be modified by the molecular
weight of chitosan. In conclusion, the molecular weight of chitosan had a major influence on formation, physical properties,
and drug release from the obtained pellets.
Published: August 10, 2007 相似文献
18.
The aim of this study was to formulate and characterize a microparticulate system of progestin-only contraceptive. Another
objective was to evaluate the effect of gamma radio-sterilization on in vitro and in vivo drug release characteristics. Levonorgestrel (LNG) microspheres were fabricated using poly(lactide-co-glycolide) (PLGA) by a novel solvent evaporation technique. The formulation was optimized for drug/polymer ratio, emulsifier
concentration, and process variables like speed of agitation and evaporation method. The drug to polymer ratio of 1:5 gave
the optimum encapsulation efficiency. Speed of agitation influenced the spherical shape of the microparticles, lower speeds
yielding less spherical particles. The speed did not have a significant influence on the drug payloads. A combination of stabilizers
viz. methyl cellulose and poly vinyl alcohol with in-water solvent evaporation technique yielded microparticles without any free
drug crystals on the surface. This aspect significantly eliminated the in vitro dissolution “burst effect”. The residual solvent content was well within the regulatory limits. The microparticles passed
the test for sterility and absence of pyrogens. In vitro dissolution conducted on the product before and after gamma radiation sterilization at 2.5 Mrad indicated no significant
difference in the drug release patterns. The drug release followed zero-order kinetics in both static and agitation conditions
of dissolution testing. The in vivo studies conducted in rabbits exhibited LNG release up to 1 month duration with drug levels maintained within the effective
therapeutic window. 相似文献
19.
A newly available polyvinylacetate aqueous dispersion, Kollicoat SR 30D, was evaluated with respect to its ability to modulate
the in vitro release of a highly water-soluble model compound (diphenhydramine hydrochloride) from nonpareil-based systems.
Kollicoat SR 30D premixed with a selected plasticizer (10% wt/wt propylene glycol, 2.5% triethyl citrate, or 2.5% dibutyl
sebacute), talc, and red #30 lake dye was coated onto the drug beads in an Aeromatic Strea I fluid-bed drier with a Wurster
insert using bottom spray. With propylene glycol as the plasticizer, increases in polymer coating level retarded drug release
from beads in a stepwise fashion along with apparent permeability, indicating a consistent release mechanisms. Stability studies
at 40°C/75% RH revealed gradual decreases in dissolution rate, and additional curing studies further confirmed the dependence
of release kinetics on curing condition. Furthermore, the type of plasticizer was found to play a key role. Unplasticized
formulations exhibited the fastest dissolution, followed by formulations plasticized with triethyl citrate, propylene glycol,
and dibutyl sebacate. All 4 formulations (unplasticized and plasticized), nevertheless, revealed a marked difference between
uncured and cured dissolution profiles. Kollicoat SR 30D has, thereby, been demonstrated to effectively retard drug release
from nonpareilbased systems. However, selected plasticizer type and subsequent curing condition play important roles in controlling
drug release from such a system. 相似文献
20.
Nanostructured agglomerated vesicles encapsulating ciprofloxacin were evaluated for modulated delivery from the lungs in a healthy rabbit model. An aliphatic disulfide crosslinker, cleavable by cysteine was used to form cross-links between nanosized liposomes to form the agglomerates. The blood levels of drug after pulmonary instillation of free ciprofloxacin, liposomal ciprofloxacin, and the agglomerated liposomes encapsulating ciprofloxacin were evaluated. The liposomes and agglomerated vesicles showed extended release of drug into the blood over 24 hours, while the free ciprofloxacin did not. The agglomerates also allowed modulation of the drug release rate upon the introduction of cysteine into the lungs post-drug instillation; the cysteine-cleavable agglomerates accelerated their drug release rate, indicated by an increased level of drug in the blood. This technology holds promise for the post-administration modulation of antibiotic release, for the prevention and treatment of pulmonary and systemic infections. 相似文献