共查询到20条相似文献,搜索用时 31 毫秒
1.
Atul C. Badhan Rajashree C. Mashru Punit P. Shah Arti R. Thakkar Nitin B. Dobaria 《AAPS PharmSciTech》2009,10(2):459-467
In the present work, sustained release gastroretentive minimatrices of amoxicillin have been designed and optimized using
central composite design. Effect of amount of xanthan gum, rate controlling polymers (HPMC K100M CR/PEO coagulant (1:1)),
carbopol 974P, and gas generating couple (sodium bicarbonate/citric acid (3:1)) was studied on dependent (response) variables,
i.e., buoyancy lag time, drug release at 1 h, time required for 95% drug release, swelling index, and bioadhesive strength.
Minimatrices were prepared by non aqueous granulation method using solution of PVP K30 in isopropyl alcohol. All the formulations
were found to contain 99.2% to 100.9% of amoxicillin per minimatrix. Optimum formulation (Formulation number AGT09) containing
high level of the independent variables was having buoyancy lag time of 7 min and drug release at 1 h was 32.5%. It required
9.39 h for 95% drug release while swelling index and bioadhesive strength were 341 and 17.9 dyn/cm2, respectively. This formulation was said to be optimum because it has minimum buoyancy lag time, requires maximum time for
95% drug release, and has higher bioadhesive capabilities. In vitro results of an optimized formulation indicate its sustained drug release and gastric retention capability, which may be very
useful for effective treatment of H. pylori infection. 相似文献
2.
The purpose of this study was to investigate the combined influence of three-level, three-factor variables on the formulation
of dacarbazine (a water-soluble drug) loaded cubosomes. Box–Behnken design was used to obtain a second-order polynomial equation
with interaction terms to predict response values. In this study, the selected and coded variables X
1, X
2, and X
3 representing the amount of monoolein, polymer, and drug as the independent variables, respectively. Fifteen runs of experiments
were conducted, and the particle size (Y
1) and encapsulation efficiency (Y
2) were evaluated as dependent variables. We performed multiple regression to establish a full-model second-order polynomial
equation relating independent and dependent variables. A second-order polynomial regression model was constructed for Y
1 and confirmed by performing checkpoint analysis. The optimization process and Pareto charts were obtained automatically,
and they predicted the levels of independent coded variables X
1, X
2, and X
3 (−1, 0.53485, and −1, respectively) and minimized Y
1 while maximizing Y
2. These corresponded to a cubosome formulation made from 100 mg of monoolein, 107 mg of polymer, and 2 mg with average diameter
of 104.7 nm and an encapsulation efficiency of 6.9%. The Box–Behnken design proved to be a useful tool to optimize the particle
size of these drug-loaded cubosomes. For encapsulation efficiency (Y
2), further studies are needed to identify appropriate regression model. 相似文献
3.
The purpose of this work was to develop and optimize gliclazide-loaded alginate–methyl cellulose mucoadhesive microcapsules
by ionotropic gelation using central composite design. The effect of formulation parameters like polymer blend ratio and cross-linker
(CaCl2) concentration on properties of gliclazide-loaded alginate–methyl cellulose microcapsules like drug encapsulation efficiency
and drug release were optimized. The optimized microcapsules were subjected to swelling, mucoadhesive, and in vivo studies. The observed responses coincided well with the predicted values from the optimization technique. The optimized microcapsules
showed high drug encapsulation efficiency (83.57 ± 2.59% to 85.52 ± 3.07%) with low T
50% (time for 50% drug release, 5.68 ± 0.09 to 5.83 ± 0.11 h). The in vitro drug release pattern from optimized microcapsules was found to be controlled-release pattern (zero order) with case II transport
release mechanism. Particle sizes of these optimized microcapsules were 0.767 ± 0.085 to 0.937 ± 0.086 mm. These microcapsules
also exhibited good mucoadhesive properties. The in vivo studies on alloxan-induced diabetic rats indicated the significant hypoglycemic effect that was observed 12 h after oral
administration of optimized mucoadhesive microcapsules. The developed and optimized alginate–methyl cellulose microcapsules
are suitable for prolonged systemic absorption of gliclazide to maintain lower blood glucose level and improved patient compliance. 相似文献
4.
Stomach-Specific Controlled Release Gellan Beads of Acid-Soluble Drug Prepared by Ionotropic Gelation Method 总被引:1,自引:0,他引:1
The purpose of the present work was the development and evaluation of stomach-specific controlled release mucoadhesive drug
delivery system prepared by ionotropic gelation of gellan beads, containing acid-soluble drug amoxicillin trihydrate, using
32 factorial design with concentration of gellan gum and quantity of drug as variables. The study showed that beads prepared
in alkaline cross-linking medium have higher entrapment efficiency than the acidic cross-linking medium. The entrapment efficiency
was in the range of 32% to 46% w/w in acidic medium, which increased up to 60% to 90% w/w in alkaline medium. Batches with lowest, medium, and highest drug entrapment were subjected to chitosan coating to form a
polyelectrolyte complex film. As polymer concentration increases, entrapment efficiency and particle size increases. Scanning
electron microscopy revealed spherical but rough surface due to leaching of drug in acidic cross-linking solution, dense spherical
structure in alkaline cross-linking solution, and rough surface of chitosan-coated beads with minor wrinkles. The in vitro drug release up to 7 h in a controlled manner following the Peppas model (r = 0.9998). In vitro and in vivo mucoadhesivity study showed that beads have good mucoadhesivity and more than 85% beads remained adhered to stomach mucosa
of albino rat even after 7 h. In vitro growth inhibition study showed complete eradication of Helicobacter pylori. These results indicate that stomach-specific controlled release mucoadhesive system of amoxicillin gellan beads may be useful
in H. pylori treatment. 相似文献
5.
Bajerová M Krejčová K Rabišková M Muselík J Dvořáčková K Gajdziok J Masteiková R 《AAPS PharmSciTech》2011,12(4):1348-1357
The aim of this study was to develop novel hydrogel-based beads and characterize their potential to deliver and release a
drug exhibiting pH-dependent solubility into distal parts of gastrointestinal (GI) tract. Oxycellulose beads containing diclofenac
sodium as a model drug were prepared by the ionotropic external gelation technique using calcium chloride solution as the
cross-linking medium. Resulting beads were characterized in terms of particle shape and size, encapsulation efficacy, swelling
ability and in vitro drug release. Also, potential drug–polymer interactions were evaluated using Fourier transform infrared spectroscopy. The
particle size was found to be 0.92–0.96 mm for inactive (oxycellulose only) and 1.47–1.60 mm for active (oxycellulose–diclofenac
sodium) beads, respectively. In all cases, the sphericity factor was between 0.70 and 0.81 with higher values observed for
samples containing higher polymer and drug concentrations. The swelling of inactive beads was found to be strongly influenced
by the pH and composition (i.e. Na+ concentration) of the selected media (simulated gastric fluid vs. phosphate buffer pH 6.8). The encapsulation efficiency of the prepared particles ranged from 58% to 65%. Results of dissolution
tests showed that the drug loading inside of the particles influenced the rate of its release. In general, prepared particles
were able to release the drug within 12–16 h after a lag time of 4 h. Fickian diffusion was found as the predominant drug release mechanism. Thus, this novel particulate system showed
a good potential to deliver drugs specifically to the distal parts of the human GI tract. 相似文献
6.
Ramesh Gannu Chinna Reddy Palem Shravan Kumar Yamsani Vamshi Vishnu Yamsani Madhusudan Rao Yamsani 《AAPS PharmSciTech》2010,11(2):976-985
The purpose of the present study was to develop and optimize reservoir-based transdermal therapeutic system (TTS) for buspirone
(BUSP), a low bioavailable drug. A three-factor, three-level Box–Behnken design was employed to optimize the TTS. Hydroxypropyl
methylcellulose, d-limonene and propylene glycol were varied as independent variables; cumulative amount permeated across rat abdominal skin
in 24 h, flux and lag time were selected as dependent variables. Mathematical equations and response surface plots were used
to relate the dependent and independent variables. The statistical validity of polynomials was established, and optimized
formulation factors were selected by feasibility and grid search. Validation of the optimization study with seven confirmatory
runs indicated high degree of prognostic ability of response surface methodology. BUSP-OPT (optimized formulation) showed
a flux 104.6 μg cm−2 h−1, which could meet target flux. The bioavailability studies in rabbits showed that about 2.65 times improvement (p < 0.05) in bioavailability, after transdermal administration of BUSP-OPT compared to oral solution. The ex vivo–in vivo correlation was found to have biphasic pattern and followed type A correlation. Reservoir-based TTS for BUSP was developed
and optimized using Box–Behnken statistical design and could provide an effective treatment in the management of anxiety. 相似文献
7.
Praveen Sher Ganesh Ingavle Surendra Ponrathnam Pankaj Poddar Atmaram P. Pawar 《AAPS PharmSciTech》2009,10(2):547-558
The purpose of this research work was to explore an application of uncoated porous drug carrier prepared by single-step drug
adsorption for a delivery system based on integration of floating and pulsatile principles intended for chronotherapy. This
objective was achieved by utilizing 32 factorial design, solvent volume (X
1) and drug amount (X
2) as selected variables, for drug adsorption using solvents, methanol, and dichloromethane (DCM), of varying polarity. Nitrogen
adsorption (N2), scanning electron microscopy of cross-sections, and atomic force microscopy were done to study adsorption patterns and
their effect on release pattern. Drug release study was customized by performing for 6 h in acidic environment to mimic gastroretention
followed by basic environment akin to transit phase. Correlation between porous data from mercury and N2 adsorption was probably studied for the first time. Observed regression analysis values for pore volume, surface area, and
drug release indicated the influence of selected variables. Total release range in acidic medium was 12.77–24.57% for methanol,
8.79–15.26% for DCM, and final release of 69.45–92.23% for methanol, and 60.16–99.99% for DCM influenced by varying internal
geometries was observed. Present form of drug delivery system devoid of any additives/excipients influencing drug release
shows distinct behavior from other approaches/technologies in chronotherapy by (a) observing desired low drug release (8%)
in acidic medium, (b) overcoming the limitations of process variables caused by multiple formulation steps and different characteristic
polymers, (c) reducing time consumption due to single step process, and (d) extending as controlled/extended release. 相似文献
8.
Sibanda W Pillay V Danckwerts MP Viljoen AM van Vuuren S Khan RA 《AAPS PharmSciTech》2004,5(1):128-141
A Plackett-Burman design was employed to develop and optimize a novel crosslinked calcium-aluminum-alginatepectinate oilisphere
complex as a potential system for the in vitro site-specific release ofMentha piperita, an essential oil used for the treatment of irritable bowel syndrome. The physicochemical and textural properties (dependent
variables) of this complex were found to be highly sensitive to changes in the concentration of the polymers (0%–1.5% wt/vol),
crosslinkers (0%–4% wt/vol) and crosslinking reaction times (0.5–6 hours) (independent variables). Particle size analysis
indicated both unimodal and bimodal populations with the highest frequency of 2 mm oilispheres. Oil encapsulation ranged from
6 to 35 mg/100 mg oilispheres. Gravimetric changes of the crosslinked matrix indicated significant ion sequestration and loss
in an exponential manner, while matrix erosion followed Higuchi's cube root law. Among the various measured responses, the
total fracture energy was the most suitable optimization objective (R
2 =0.88, Durbin-Watson Index=1.21%, Coefficient of Variation (CV)=33.21%). The Lagrangian technique produced no significant
differences (P>.05) between the experimental and predicted total fracture energy values (0.0150 vs 0.0107 J). Artificial Neural Networks,
as an alternative predictive tool of the total fracture energy, was highly accurate (final mean square error of optimal network
epoch≈0.02). Fused-coated optimized oilispheres produced a 4-hour lag phase followed by zero-order kinetics (n>0.99), whereby
analysis of release data indicated that diffusion (Fickian constantk
1=0.74 vs relaxation constantk
2=0.02) was the predominant release mechanism. 相似文献
9.
The objective of this study was to develop solid lipid nanoparticles (SLNs) of simvastatin and to optimize it for independent
variables (amount of glycerol monostearate, concentration of poloxamer, and volume of isopropyl alcohol) in order to achieve
desired particle size with maximum percent entrapment efficiency (% EE) and percent cumulative drug release (% CDR). To achieve
our goal, eight formulations (F
1–F
8) of SLNs were prepared by solvent injection technique and optimized by 23 full-factorial design. The design was validated by extra design checkpoint formulation (F
9), and the possible interactions between independent variables were studied. The responses of the design were analyzed using
Design Expert 7.1.6. (Stat-Ease, Inc, USA), and the analytical tools of software were used to draw Pareto charts and response
surface plots. On the basis of software analysis, formulation F
10 with a desirability factor of 0.611 was selected as optimized formulation and was evaluated for the independent parameters.
Optimized formulation showed particle size of 258.5 nm, % EE of 75.81%, with of 82.67% CDR after 55 h. The release kinetics
of the optimized formulation best fitted the Higuchi model, and the recrystallization index of optimized formulation was found
to be 65.51%. 相似文献
10.
Praveen Sher Ganesh Ingavle Surendra Ponrathnam James R. Benson Nai-Hong Li Atmaram P. Pawar 《AAPS PharmSciTech》2009,10(4):1368-1380
The aim of the present study was to design a novel/conceptual delivery system using ibuprofen, anticipated for chronotherapy
in arthritis with porous material to overcome the formulation limits (multiple steps, polymers, excipients) and to optimize
drug loading for a desired release profile suitable for in vitro investigations. The objective of this delivery system lies in the availability of maximum drug amount for absorption in the
wee hours as recommended. Drug loading using 32 factorial design on porous carrier, synthesized by high internal phase emulsion technique using styrene and divinylbenzene,
was done via solvent evaporation using methanol and dichloromethane. The system was evaluated in vitro for drug loading, encapsulation efficiency, and surface characterization by scanning electron, atomic force microscopy, and
customized drug release study. This study examined critical parameters such as solvent volume, drug amount, and solvent polarity
on investigations related to drug adsorption and release mostly favoring low-polarity solvent dichloromethane. Overall release
in all batches ranged 0.98–52% in acidic medium and 71–94% in basic medium. These results exhibit uniqueness in achieving
the least drug release of 0.98%, an ideal one, without using any release modifiers, making it distinct from other approaches/technologies
for time and controlled release and for chronotherapy. 相似文献
11.
The purpose of the present study was to design mucoadhesive gliadin nanoparticles (GNP) containing amoxicillin and to evaluate
their effectiveness in eradicating Helicobacter pylori. GNP-bearing amoxicillin (AGNP) was prepared by desolvation method. The effect of process variables such as gliadin concentration
and initial drug loading on particle size, shape, percent payload, percent entrapment efficiency, in vitro release profile,
and mucoadhesive property of GNP was assessed. Rhodamine isothiocyanate-entrapped GNP formulations were prepared to evaluate
their in vivo gastric mucoadhesive property in albino rats. With increasing gliadin concentration, the mucoadhesive property
of GNP increased. Typically, the maximum amount of nanoparticles remaining was 82±4%, which represented a stronger mucoadhesive
propensity and specificity of GNP toward the stomach. In vitro antimicrobial activity of AGNP was evaluated by growth inhibition
studies on an isolated H pylori strain. The time required for complete eradication was higher in AGNP than in amoxicillin because of the controlled drug
delivery of amoxicillin from AGNP. In vivo clearance of H pylori following oral administration of AGNP to infected Mongolian gerbils was examined. Amoxicillin and AGNP both showed anti-H pylori effects in this experimental model of infection, but the required dose for complete eradication was less in AGNP than in
amoxicillin. In conclusion, AGNP eradicated H pylori from the gastrointestinal tract more effectively than amoxicillin because of the prolonged gastrointestinal residence time
attributed to mucoadhesion. A dosage form containing mucoadhesive nanoparticles bearing a potential antibiotic should be useful
for the complete eradication of H pylori. 相似文献
12.
The aim of the current study was to design oral controlled release mucoadhesive compressed hydrophilic matrices of atenolol
and to optimize the drug release profile and bioadhesion using response surface methodology. Tablets were prepared by direct
compression and evaluated for bioadhesive strength and in vitro dissolution parameters. A central composite design for 2 factors
at 3 levels each was employed to systematically optimize drug release profile and bioadhesive strength. Carbopol 934P and
sodium carboxymethylcellulose were taken as the independent variables. Response surface plots and contour plots were drawn,
and optimum formulations were selected by feasibility and grid searches. Compressed matrices exhibited non-Fickian drug release
kinetics approaching zero-order, as the value of release rate exponent (n) varied between 0.6672 and 0.8646, resulting in regulated and complete release until 24 hours. Both the polymers had significant
effect on the bioadhesive strength of the tablets, measured as force of detachment against porcine gastric mucosa (P<.001). Polynomial mathematical models, generated for various response variables using multiple linear regression analysis,
were found to be statistically significant (P<.01). Validation of optimization study, performed using 8 confirmatory runs, indicated very high degree of prognostic ability
of response surface methodology, with mean percentage error (±SD) as −0.0072±1.087. Besides unraveling the effect of the 2
factors on the various response variables, the study helped in finding the optimum formulation with excellent bioadhesive
strength and controlled release.
Published: January 13, 2006 相似文献
13.
Sustained release mucoadhesive amoxicillin tablets with tolerance to acid degradation in the stomach were studied. The sustained-release
tablets of amoxicillin were prepared from amoxicillin coated with ethyl cellulose (EC) and then formulated into tablets using
chitosan (CS) or a mixture of CS and beta-cyclodextrin (CD) as the retard polymer. The effects of various (w/w) ratios of EC/amoxicillin, the particle sized of EC coated amoxicillin and the different (w/w) ratios of CS/CD for the retard polymer, on the amoxicillin release profile were investigated. The physicochemical properties
of the EC coated amoxicillin particles and tablets were determined by scanning electron microscopy, Fourier-transform infrared
spectroscopy, X-ray diffraction, and differential scanning calorimetry. The result showed that the release profiles of amoxicillin
were greatly improved upon coating with EC, while the inclusion of CD to the CS retardant additionally prolonged the release
of the drug slightly. Overall, a sustained release of amoxicillin was achieved using amoxicillin coated with EC at a (w/w) ratio of 1:1 and a particle size of 75–100 μm. Therefore, the tablet formulation of amoxicillin may be an advantageous alternative
as an orally administered sustained-release formulation for the treatment of peptic ulcers. 相似文献
14.
The purpose of this research was to prepare a floating drug delivery system of diltiazem hydrochloride (DTZ). Floating matrix
tablets of DTZ were developed to prolong gastric residence time and increase its bioavailability. Rapid gastrointestinal transit
could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy
of the administered dose. The tablets were prepared by direct compression technique, using polymers such as hydroxypropylmethylcellulose
(HPMC, Methocel K100M CR), Compritol 888 ATO, alone or in combination and other standard excipients. Sodium bicarbonate was
incorporated as a gas-generating agent. The effects of sodium bicarbonate and succinic acid on drug release profile and floating
properties were investigated. A 32 factorial design was applied to systematically optimize the drug release profile. The amounts of Methocel K100M CR (X1) and Compritol 888 ATO (X2) were selected as independent variables. The time required for 50% (t50) and 85% (t85) drug dissolution were selected as dependent variables. The results of factorial design indicated that a high level of both
Methocel K100M CR (X1) and Compritol 888 ATO (X2) favors the preparation of floating controlled release of DTZ tablets. Comparable release profiles between the commercial
product and the designed system were obtained. The linear regression analysis and model fitting showed that all these formulations
followed Korsmeyer and Peppas model, which had a higher value of correlation coefficient (r). While tablet hardness had little or no effect on the release kinetics and was found to be a determining factor with regards
to the buoyancy of the tablets.
Published: September 7, 2007 相似文献
15.
Bovine serum albumin-loaded beads were prepared by ionotropic gelation of alginate with calcium chloride and chitosan. The
effect of sodium alginate concentration and chitosan concentration on the particle size and loading efficacy was studied.
The diameter of the beads formed is dependent on the size of the needle used. The optimum condition for preparation alginate–chitosan
beads was alginate concentration of 3% and chitosan concentration of 0.25% at pH 5. The resulting bead formulation had a loading
efficacy of 98.5% and average size of 1,501 μm, and scanning electron microscopy images showed spherical and smooth particles.
Chitosan concentration significantly influenced particle size and encapsulation efficiency of chitosan–alginate beads (p < 0.05). Decreasing the alginate concentration resulted in an increased release of albumin in acidic media. The rapid dissolution
of chitosan–alginate matrices in the higher pH resulted in burst release of protein drug. 相似文献
16.
Several matrix tablet formulations (hydrophilic-based, wax-based, and three-layer tablets) were designed for controlling the
release of the highly water soluble drug, venlafaxine hydrochloride (VenHCl) for once-daily administration. The three-layer
tablets consist of non-swellable, compritol-based middle layers containing the drug to which hydrophilic top and bottom barrier
layers were applied. A 23 full-factorial design was employed for optimization and to explore the effect of different variables on the release rate
of the drug from the three-layer tablets. The optimized levels of each independent variable were based on the criterion of
desirability. The calculated values of f
1
and f
2
were 4.131 and 79.356, respectively; indicating that the release profile of the optimized PEO layered tablet formulation
is comparable to that of the target release model. The pharmacokinetic parameters of VenHCl from the optimized three-layer
tablet was compared to the marketed extended release capsule as a reference in healthy human subjects using a randomized crossover
design. In this study, the 90% confidence interval for AUC0–24 and AUC0−∞ are within (0.8–1.25), which satisfied the bioequivalence criteria. It could be concluded that a promising once-daily extended-release
three-layer tablet of the highly water soluble drug, VenHCl, was successfully designed. 相似文献
17.
Li GY Zhong M Zhou ZD Zhong YD Ding P Huang Y 《International journal of biological macromolecules》2011,49(5):970-978
The aims of this investigation were to develop a procedure to prepare chelerythrine (CHE) loaded O-carboxymethylchitosan (O-CMCS) microspheres by emulsion cross-linking method and optimize the process and formulation variables using response surface methodology (RSM) with a three-level, three-factor Box-Behnken design (BBD). The independent variables studied were O-CMCS/CHE ratio, O/W phase ratio, and O-CMCS concentration, dependent variables (responses) were drug loading content and encapsulation efficiency. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The process and formulation variables were optimized to achieve maximum drug loading content and entrapment efficiency by the desirability function. The optimized microsphere formulation was characterized for particle size, shape, morphology and in vitro drug release. Results for mean particle size, drug loading content, entrapment efficiency, and in vitro drug release of CHE-loaded O-CMCS microspheres were found to be of 12.18 μm, 4.16 ± 3.36%, 57.40 ± 2.30%, and 54.5% at pH 7.4 after 70 h, respectively. The combination use of RSM, BBD and desirability function could provide a promising application for O-CMCS as controlled drug delivery carrier and help to develop procedures for a lab-scale microemulsion process. 相似文献
18.
Interpolyelectrolyte (IPE) complexation between carrageenan (CG) and Eudragit E (EE) was studied in 0.1 M HCl and was used
to develop floating matrix tablets aimed to prolong gastric-residence time and sustain delivery of the loaded drug. The optimum
EE/CG IPE complexation weight ratio (0.6) was determined in 0.1 M HCl using apparent viscosity measurements. The IPE complex
was characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. Metronidazole matrix tablets
were prepared by direct compression using EE, CG, or hybrid EE/CG with ratio optimal for IPE complexation. Corresponding effervescent
tablets were prepared by including Na bicarbonate as an effervescent agent. Tablets were evaluated for in vitro buoyancy and drug release in 0.1 M HCl. Both CG and EE–CG effervescent matrices (1:2 drug to polymer weight ratio, 60 mg
Na bicarbonate) achieved fast and prolonged floating with floating lag times less than 30 s and floating duration of more
than 10 h. The corresponding EE effervescent matrices showed delayed floating and rapid drug release, and completely dissolved
after 3 h of dissolution. CG matrices showed an initial burst drug release (48.3 ± 5.0% at 1 h) followed by slow drug release
over 8 h. EE–CG matrices exhibited sustained drug release in almost zero-order manner for 10 h (68.2 ± 6.6%). The dissolution
data of these matrices were fitted to different dissolution models. It was found that drug release followed zero-order kinetics
and was controlled by the superposition of the diffusion and erosion. 相似文献
19.
The aim of this work was the formulation and characterization of alginate (ALG)–doxycycline (DOX) hydrogel microparticles
(MPs) embedded into Pluronic F127 thermogel for DOX intradermal sustained delivery. ALG–DOX MPs were formed by adding a solution
of the drug into a 1.5% polymer solution while stirring. The MPs were cross-linked by dispersion into a 1.2% CaCl2 solution. Free MPs were characterized in terms of size, drug content, and release behavior by HPLC and UV–vis. DOX and hydrogel
MPs were embedded into PF127, PF127-HPMC, and PF127-Methocel thermogels. The thermogels were characterized in terms of gelling
time, morphology, and release behavior. A target release period of 4–7 days was considered optimal. The hydrogel MPs were
about 20 μm in size with 90% of the population <59 μm. Drug content was about 35% (w/w). DOX released rapidly from the MPs, 90% within 2 days. An expected faster release was observed for free DOX from the thermogels
with 80–90% of drug released after 3.5–4 h even in the presence of 1% HPMC or Methocel. The release was sustained after embedding
the MPs into PF127 and PF127-HPMC thermogels. In particular, the PF127-HPMC thermogel showed an almost linear release, reaching
80% after 3 days and 90% up to 6 days. Although a further characterization and formulation assessment is required to optimize
MP characteristics, ALG/DOX-loaded hydrogel MPs, when embedded into a PF127-HPMC thermogel, show a potential for achieving
a 7-day sustained release formulation for DOX intradermal delivery. 相似文献
20.
The purpose of this research was to design oral controlled release (CR) matrix tablets of zidovudine (AZT) using hydroxypropyl
methylcellulose (HPMC), ethyl cellulose (EC) and carbopol-971P (CP) and to study the effect of various formulation factors
on in vitro drug release. Release studies were carried out using USP type 1 apparatus in 900 ml of dissolution media. Release kinetics
were analyzed using zero-order, Higuchi’s square root and Ritger–Peppas’ empirical equations. Release rate decreased with
increase in polymer proportion and compression force. The release rate was lesser in formulations prepared using CP (20%)
as compared to HPMC (20%) as compared to EC (20%). No significant difference was observed in the effect of pH of dissolution
media on drug release from formulations prepared using HPMC or EC, but significant difference was observed in CP based formulations.
Decrease in agitation speed from 100 to 50 rpm decreased release rate from HPMC and CP formulations but no significant difference
was observed in EC formulations. Mechanism of release was found to be dependent predominantly on diffusion of drug through
the matrix than polymer relaxation incase of HPMC and EC formulations, while polymer relaxation had a dominating influence
on drug release than diffusion incase of CP formulations. Designed CR tablets with pH independent drug release characteristics
and an initial release of 17–25% in first hour and extending the release up to 16–20 h, can overcome the disadvantages associated
with conventional tablets of AZT. 相似文献