Mucoadhesive, thermosensitive, prolonged-release vaginal gel for clotrimazole:beta-cyclodextrin complex

The purpose of this study was to achieve a better therapeutic efficacy and patient compliance in the treatment for vaginitis. Clotrimazole (1%) has been formulated in a vaginal gel using the thermosensitive polymer Pluronic F127 (20%) together with mucoadhesive polymers such as Carbopol 934 and hydroxypropylmethylcellulose (0.2% for both). To increase its aqueous solubility, clotrimazole was incorporated as its inclusion complex with 1:1 molar ratio with beta-cyclodextrin. The inclusion complex was thoroughly characterized using various techniques, including 1H NMR spectroscopy, FT IR spectrophotometry, differential scanning calorimetry, scanning electron microscopy, phase solubility studies, and determination of stability constant (k(1:1)). The gelation temperature and rheological behavior of different formulations at varying temperatures were measured. In vitro release profiles of the gels were determined in pH 5.5 citrate buffer. It was observed that complexation with cyclodextrin slowed down the release of clotrimazole considerably. Carbopol 934, on the other hand, was found to interact with beta-cyclodextrin, inducing precipitation. As far as rheological properties are concerned, thermosensitive in situ gelling was obtained with formulations containing drug:cyclodextrin complex rather than with free drug. Thus, the optimum formulation for a controlled-release thermosensitive and mucoadhesive vaginal gel was determined to be clotrimazole:beta-cyclodextrin 1% with 0.2% hydroxypropylmethylcellulose in Pluronic F127 gel (20%) providing continuous and prolonged release of active material above MIC values.     

Mucoadhesive, thermosensitive, prolonged-release vaginal gel for clotrimazole: β-cyclodextrin complex

The purpose of this study was to achieve a better therapeutic efficacy and patient compliance in the treatment for vaginitis. Clotrimazole (1%) has been formulated in a vaginal gel using the thermosensitive polymer Pluronic F127 (20%) together with mucoadhesive polymers such as Carbopol 934 and hydroxypropylmethylcellulose (0.2% for both). To increase its aqueous solubility., clotrimazole was incorporated as its inclusion complex with 1∶1 molar ratio with β-cyclodextrin. The inclusion complex was thoroughly characterized using various techniques, including ¹H NMR spectroscopy, FT IR spectrophotometry, differential scanning calorimetry, scanning electron microscopy, phase solubility studies, and determination of stability constant (k_1∶1). The gelation temperature and rheological behavior of different formulations at varying temperatures were measured. In vitro release profiles of the gels were determined in pH 5.5 citrate buffer. It was observed that complexation with cyclodextrin slowed down the release of clotrimazole considerably. Carbopol 934, on the other hand, was found to interact with β-cyclodextrin, inducing precipitation. As far as rheological properties are concerned, thermosensitive in situ gelling was obtained with formulations containing drug: cyclodextrin complex rather than with free drug. Thus, the optimum formulation for a controlled-release thermosensitive and mucoadhesive vaginal gel was determined to be clotrimazole: β-cyclodextrin 1% with 0.2% hydroxypropylmethylcellulose in Pluronic F127 gel (20%) providing continuous and prolonged release of active material above MIC values.     

Development and Evaluation of oral multiple-unit and single-unit hydrophilic controlled-release systems

This study compared the release behavior of single-unit (tablets, capsules) and multiple-unit (minitablets in capsules) controlled-release systems of furosemide. The swelling and erosion behaviors of these systems, which contained the swellable hydrophilic polymers sodium alginate (high viscosity) and Carbopol 974P, were compared. Swelling and erosion experiments showed a high degree of swelling and limited erosion for the Carbopol preparations, whereas less swelling but greater erosion was observed for the sodium alginate preparations. The sodium alginate preparations were eroded in 6 hours, while Carbopol preparations exhibited limited erosion within this period of time. These results appear to be attributed to the physicochemical characteristics of the polymers used in this study. Polymer characteristics greatly influenced the release of furosemide (model drug) from the formulations prepared and tested. Sodium alginate had a less pronounced sustained release effect compared with Carbopol (ie, in 8 hours all 3 sodium alginate dosage forms displayed complete release of furosemide, while only 30% of the drug was released from Carbopol dosage forms). Finally, all 3 Carbopol dosage forms (single- and multiple-unit) displayed similar release behavior while sodium alginate dosage forms displayed a different and more distinctive behavior. Minitablets and tablets showed a greater sustained release effect compared with capsules. Evaluation of the release data indicates that the release mechanism for sodium alginate formulations may be attributed to erosion/dissolution, while for Carbopol it may be attributed mainly to polymer relaxation and diffusion of the drug from the polymer surface.     

Mucoadhesive bilayer tablets of propranolol hydrochloride

The purpose of this research was to study mucoadhesive bilayer buccal tablets of propranolol hydrochloride using the bioadhesive polymers sodium alginate (Na-alginate) and Carbopol 934P (CP) along with ethyl cellulose as an impermeable backing layer. The tablets were evaluated for weight variation, thickness, hardness, friability, surface pH, mucoadhesive strength, swelling index, in vitro drug release, ex vivo drug permeation, ex vivo mucoadhesion, and in vivo pharmacodynamics in rabbits. Tablets containing Na-alginate and CP in the ratio of 5∶1 (F2) had the maximum percentage of in vitro drug release without disinte-gration in 12 hours. The swelling index was proportional to Na-alginate content and inversely proportional to CP content. The surface pH of all tablets was found to be satis-factory (7.0±1.5), close to neutral pH; hence, buccal cavity irritation should not occur with these tablets. The mechanism of drug release was found to be non-Fickian diffusion and followed zero-order kinetics. The formulation F4 was optimized based on good biodhesive strength (28.9±0.99 g) and sustained in vitro drug permeation (68.65%±3.69% for 12 hours). The behavior of formulation F4 was examined in human saliva, and both the drug and the buccal tablet were found to be stable. The formulation F4 was applied to rabbit oral mucosa for in vivo studies. The formulation inhibited isoprenaline-induced tachycardia. The studies conducted in rabbits confirmed the sustained release as compared with intravenous administration. Published: September 21, 2007     

Development and Evaluation of Buccoadhesive Controlled Release Tablets of Lercanidipine

The purpose of this research was to develop and evaluate buccal mucoadhesive controlled release tablets of lercanidipine hydrochloride using polyethylene oxide and different viscosity grades of hydroxypropyl methylcellulose individually and in combination. Effect of polymer type, proportion and combination was studied on the drug release rate, release mechanism and mucoadhesive strength of the prepared formulations. Buccal mucoadhesive tablets were made by direct compression and were characterized for content uniformity, weight variation, friability, surface pH, thickness and mechanism of release. In order to estimate the relative enhancement in bioavailability one optimized formulation was evaluated in rabbits. Further, placebo tablets were also evaluated for acceptability in human subjects. Results indicated acceptable physical characteristics of designed tablets with good content uniformity and minimum weight variation. Drug release and mucoadhesive strength were found to depend upon polymer type, proportion and viscosity. The formulations prepared using poly ethylene oxide gave maximum mucoadhesion. The release mechanism of most formulations was found to be of anomalous non-Fickian type. In vivo studies of selected formulation in rabbits demonstrated significant enhancement in bioavailability of lercanidipine hydrochloride relative to orally administered drug. Moreover, in human acceptability studies of placebo formulations, the designed tablets adhered well to the buccal mucosa for more than 4 h without causing any discomfort. It may be concluded that the designed buccoadhesive controlled release tablets have the potential to overcome the disadvantage of poor and erratic oral bioavailability associated with the presently marketed formulations of lercanidipine hydrochloride.     

Thermoreversible-mucoadhesive Gel for nasal delivery of sumatriptan

The purpose of the present study was to develop intranasal delivery systems of sumatriptan using thermoreversible polymer Pluronic F127 (PF 127) and mucoadhesive polymer Carbopol 934P (C934P). Formulations were modulated so as to have gelation temperature below 34°C to ensure gelation at physiological temperature after intranasal administration. Gelation temperature was determined by physical appearance as well as by rheological measurement. The gelation temperatures of the formulations decreased by addition of increasing concentrations of Carbopol (ie, from 29°C for 18% PF127 to 23.9°C for 18% PF127, 0.5% Carbopol). The mucoadhesive force in terms of detachment stress, determined using sheep nasal mucosal membrane, increased with increasing concentration of Carbopol. The results of in vitro drug permeation studies across sheep nasal mucosa indicate that effective permeation coefficient could be significantly increased by using in situ gelling formulation with Carbopol concentration 0.3% or greater. Finally, histopathological examination did not detect any damage during in vitro permeation studies. In conclusion, the PF 127 gel formulation of sumatriptan, with in situ gelling and mucoadhesive properties with increased permeation rate is promising for prolonging nasal residence time and thereby nasal absorption. Published: August 4, 2006     

Effect of hydrophilic polymers on buccoadhesive eudragit patches of propranolol hydrochloride using factorial design

The purpose of this study was to develop formulations and systematically evaluate in vitro performances of buccoadhesive patches of propranolol hydrochloride using the hydrophobic polymer Eudragit L-100 as the base matrix. The hydrophilic polymers Carbopol 934 and polyvinyl pyrrolidone (PVP) K30 were incorporated into the Eudragit patches, to provide the patches with bioadhesive properties and to modify the rate of drug release. The patches, which were prepared by the solvent casting method, were smooth and elegant in appearance; were uniform in thickness, weight, and drug content; showed no visible cracks; and showed good folding endurance. A 3² full factorial design was employed to study the effect of independent variables like hydrophilic polymers Carbopol 934 and PVP K30, which significantly influenced characteristics like swelling index, ex vivo mucoadhesive strength, in vitro drug release, and ex vivo residence time. A stability study of optimized Eudragit patches was done in natural human saliva; it was found that both drug and buccal patches were stable in human saliva. It can be concluded that the present buccal formulation can be an ideal system to improve the bioavailability of the drug by avoiding hepatic first-pass metabolism. Published: June 22, 2007     

Design and in vitro and in vivo evaluation of mucoadhesive microcapsules of glipizide for oral controlled release: A technical note

Conclussion  Thus, large spherical microcapsules with a coat consisting of alginate and a mucoadhesive polymer (sodium CMC, methylcellulose, Carbopol, or HPMC) could be prepared by an orifice-ionic gelation process. The microcapsules exhibited good mucoadhesive properties in an in vitro test. Glipizide release from these mucoadhesive microcapsules was slow and extended over longer periods of time and depended on composition of the coat. Drug release was diffusion controlled and followed zero-order kinetics after a lag, period of 1 hour. In the in vivo evaluation, alginate-Carbopol microcapsules could sustain the hypoglycemic effect of glipizide over a 14-hour period. These mucoadhesive microcapsules are, thus, suitable for oral controlled release of glipizide.     

Influence of Compression Force on The Behavior of Mucoadhesive Buccal Tablets

The purpose of this research was to study the compression force influence on polymers, tablet behavior and drug release rate. Several tablet batches were produced by varying the compression force and by using hydroxyethyl cellulose (HEC) and Carbopol 940 in the 1:1 ratio as matrix forming polymers. All batches were characterized by DSC and X-ray analyses and in terms of swelling, ex vivo and in vivo mucoadhesive time, ex vivo mucoadhesion force, and in vitro and in vivo release. No significant excipient–excipient or excipient–drug interactions were observed in any of the batches. All the tablets hydrated quickly and their high hydration percentage showed that the compression forces used did not remarkably affect the water penetration and the polymeric chain stretching. Mucoadhesion performances and drug release were mainly influenced by compression force; its increase produced higher ex vivo and in vivo mucoadhesion and the in vitro and in vivo drug releases were seen to decrease with the increase of the compression force. However tablets fabricated by using the lowest compression force showed the best in vivo mucoadhesive time and hydrated faster when compared to the others. Tablets 4 and 5, prepared with the highest forces, caused pain during in vivo application and gave rise to irritation needing to be detached by the volunteers while tablet 1, prepared with the lowest force, gave the best results because it was able to produce the highest drug salivary concentration and no pain. All tablets exhibited an anomalous release mechanism.     

Formulation Study and Evaluation of Matrix and Three-layer Tablet Sustained Drug Delivery Systems Based on Carbopols with Isosorbite Mononitrate

The purpose of this research was to develop and evaluate different preparations of sustained delivery systems, using Carbopols as carriers, in the form of matrices and three-layer tablets with isosorbite mononitrate. Matrix tablets were prepared by direct compression whereas three-layer tablets were prepared by compressing polymer barrier layers on both sides of the core containing the drug. The findings of the study indicated that all systems demonstrated sustained release. The properties of the polymer used and the structure of each formulation appear to considerably affect drug release and its release rate. The three-layer formulations exhibit lower drug release compared to the matrices. This was due to the fact that the barrier-layers hindered the penetration of liquid into the core and modified drug dissolution and release. The geometrical characteristics/structure of the tablets as well as the weight/thickness of the barriers-layers considerably influence the rate of drug release and the release mechanisms. Kinetic analysis of the data indicated that drug release from matrices was mainly attributed to Fickian diffusion while three-layer tablets exhibited either anomalous diffusion or erosion/relaxation mechanisms. The advantage of Carbopol formulations is that a range of release profiles can easily be obtained through variations in tablet structure and thus Carbopols are appropriate carriers of oral sustained drug delivery systems for soluble drugs such as the isosorbite mononitrate.     

Progesterone-loaded nanosized transethosomes for vaginal permeation enhancement: formulation,statistical optimization,and clinical evaluation in anovulatory polycystic ovary syndrome

Bio-identical progesterone (PRG) is an exogenous female steroidal hormone which is used for treatment of polycystic ovary syndrome (PCOS). However, it suffers from poor bioavailability due to hepatic metabolism and poor solubility. The target of this work was to evaluate and statistically optimize PRG-loaded nanovesicle transethosomes (NVTEs) based in mucoadhesive gel for transvaginal delivery of PRG as potential luteal-phase support. A 2⁴ full factorial design was used to explore the effect of phosphatidylcholine (PC), Tween 80, cetyltrimethyl ammonium bromide and ethanol concentration on particle size, entrapment efficiency (EE%), % in vitro PRG release after 24?h and transvaginal flux. PRG-loaded NVTEs were prepared by injection sonication method. The results revealed that the mean particle sizes ranged from 133.3?±?3.42 to 349.5?±?1.24?nm, zeta potential ranged from –23.5?±?3.84 to +74.6?±?4.97?mV, EE% ranged from 87.93?±?3.58 to 97.05?±?2.61%, % PRG release ranged from 50.9?±?2.75 to 90.69?±?2.07 and transvaginal flux ranged from 0.274?±?0.03 to 0.531?±?0.04?mg/cm²/h. The optimized formulation was subjected to transmission electron microscope for morphological examination and then incorporated in the mucoadhesive vaginal gel using Carbopol 974, hydroxyl propyl methylcellulose and sodium alginate. The optimized formulation was clinically studied in anovulatory PCOS and showed a significant increase in the serum PRG, endometrial thickness, echogenicity degree and the pregnancy rate. Briefly, PRG-loaded NVTEs vaginal gel might be a promising formulation for luteal phase support and increase pregnancy rate in anovulatory PCOS.     

Design and In Vitro/In Vivo Evaluation of Novel Mucoadhesive Buccal Discs of an Antifungal Drug: Relationship Between Swelling, Erosion, and Drug Release

Two groups of fluconazole mucoadhesive buccal discs were prepared: (a) Fluconazole buccal discs prepared by direct compression containing bioadhesive polymers, namely, Carbopol 974p (Cp), sodium carboxymethyl cellulose (SCMC), or sodium alginate (SALG) in combination with hydroxypropyl methylcellulose (HPMC) or hydroxyethyl cellulose (HEC). (b) Fluconazole buccal discs prepared by freeze drying containing different polymer combinations (SCMC/HPMC, Cp/HPMC, SALG/HPMC, and chitosan/SALG). The prepared discs were evaluated by investigating their release pattern, swelling capacity, mucoadhesion properties, and in vitro adhesion time. In vivo evaluation of the buccal disc and in vivo residence times were also performed. Fluconazole salivary concentration after application of fluconazole buccal systems to four healthy volunteers was determined using microbiological assay and high-performance liquid chromatography. SCMC/HPMC buccal disc prepared by direct compression could be considered comparatively superior mucoadhesive disc regarding its in vitro adhesion time, in vivo residence time, and in vitro/in vivo release rates of the drug. Determination of the amount of drug released in saliva after application of the selected fluconazole disc confirmed the ability of the disc to deliver the drug over a period of approximately 5 h and to reduce side effects and possibility of drug interaction encountered during systemic therapy of fluconazole, which would be beneficial in the case of oral candidiasis.     

Studies on Formulation Development of Mucoadhesive Sustained Release Itraconazole Tablet Using Response Surface Methodology

The purpose of this research was to prepare and evaluate sustained release mucoadhesive tablets of Itraconazole. It is practically insoluble in aqueous fluids hence its solid dispersion with Eudragit E100 was prepared by spray drying. This was formulated in matrix of hydrophilic mucoadhesive polymers Carbopol 934P (CP) and Methocel K4M (HPMC). The formulation was optimized using a 3² factorial design. Amounts of CP and HPMC were taken as formulation variables for optimizing response variables i.e. mucoadhesion and dissolution parameters. The optimized mucoadhesive formulation was orally administered to albino rabbits, and blood samples collected were used to determine pharmacokinetic parameters. The solid dispersion markedly enhanced the dissolution rate of itraconazole. The bioadhesive strength of formulation was found to vary linearly with increasing amount of both polymers. Formulations exhibited drug release fitting Peppas model with value of n ranging from 0.61 to 1.18. Optimum combination of polymers was arrived at which provided adequate bioadhesive strength and fairly regulated release profile. The experimental and predicted results for optimum formulations were found to be in close agreement. The formulation showed C _max 1898 ± 75.23 ng/ml, t _max of the formulation was 2 h and AUC was observed to be 28604.9 ng h/ml     

Eudragit-coated pectin microspheres of 5-fluorouracil for colon targeting

An objective of the present investigation was to prepare and evaluate Eudragit-coated pectin microspheres for colon targeting of 5-fluorouracil (FU). Pectin microspheres were prepared by emulsion dehydration method using different ratios of FU and pectin (1:3 to 1:6), stirring speeds (500–2000 rpm) and emulsifier concentrations (0.75%–1.5% wt/vol). The yield of preparation and the encapsulation efficiencies were high for all pectin microspheres. Microspheres prepared by using drug:polymer ratio 1:4, stirring speed 1000 rpm, and 1.25% wt/vol concentration of emulsifying agent were selected as an optimized formulation. Eudragit-coating of pectin microspheres was performed by oil-in-oil solvent evaporation method using coat: core ratio (5:1). Pectin microspheres and Eudragit-coated pectin microspheres were evaluated for surface morphology, particle size and size distribution, swellability, percentage drug entrapment, and in vitro drug release in simulated gastrointestinal fluids (SGF). The in vitro drug release study of optimized formulation was also performed in simulated colonic fluid in the presence of 2% rat cecal content. Organ distribution study in albino rats was performed to establish the targeting potential of optimized formulation in the colon. The release profile of FU from Eudragit-coated pectin microspheres was pH dependent. In acidic medium, the release rate was much slower; however, the drug was released quickly at pH 7.4. It is concluded from the present investigation that Eudragit-coated pectin microspheres are promising controlled release carriers for colon-targeted delivery of FU. Published: February 16, 2007     

Evaluation of mucoadhesive hydrogels loaded with diclofenac sodium-chitosan microspheres for rectal administration

Considering the advantageous for the rectal administration of non-steroidal anti-inflammatory drugs, the objective of this study was to formulate and evaluate rectal mucoadhesive hydrogels loaded with diclofenac-sodium chitosan (DFS-CS) microspheres. Hydroxypropyl methylcellulose (HPMC; 5%, 6%, and 7% w/w) and Carbopol 934 (1% w/w) hydrogels containing DFS-CS microspheres equivalent to 1% w/w active drug were prepared. The physicochemical characterization revealed that all hydrogels had a suitable pH for rectal application (6.5–7.4). The consistency of HPMC hydrogels showed direct proportionality to the concentration of the gelling agent, while carbopol 934 gel showed its difficulty for rectal administration. Farrow’s constant for all hydrogels were greater than one indicating pseudoplastic flow. In vitro drug release from the mucoadhesive hydrogel formulations showed a controlled drug release pattern, reaching 34.6–39.7% after 6 h. The kinetic analysis of the release data revealed that zero-order was the prominent release mechanism. The mucoadhesion time of 7% w/w HPMC hydrogel was 330 min, allowing the loaded microspheres to be attached to the surface of rectal mucosa. Histopathological examination demonstrated the lowest irritant response to the hydrogel loaded with DFS-CS microspheres in response to other forms of the drug.     

Mucoadhesive bilayered tablets for buccal sustained release of flurbiprofen

The aim of this work was the design of sustained-release mucoadhesive bilayered tablets, using mixtures of mucoadhesive polymers and an inorganic matrix (hydrotalcite), for the topical administration of flurbiprofen in the oral cavity. The first layer, responsible for the tablet retention on the mucosa, was prepared by compression of a cellulose derivative and polyacrylic derivative blend. The second layer, responsible for buccal drug delivery, was obtained by compression of a mixture of the same (first layer) mucoadhesive polymers and hydrotalcite containing flurbiprofen. Nonmedicated tablets were evaluated in terms of swelling, mucosal adhesion, and organoleptic characteristics; in vitro and in vivo release studies of flurbiprofen-loaded tablets were performed as well. The best results were obtained from the tablets containing 20 mg of flurbiprofen, which allowed a good anti-inflammatory sustained release in the buccal cavity for 12 hours, ensuring efficacious salivary concentrations, and led to no irritation. This mucoadhesive formulation offers many advantages over buccal lozenges because it allows for reduction in daily administrations and daily drug dosage and is suitable for the treatment of irritation, pain, and discomfort associated with gingivitis, sore throats, laryngopharyngitis, cold, and periodontal surgery. Moreover, it adheres well to the gum and is simple to apply, which means that patient compliance is improved. Published: July 13, 2007     

一种白细胞介素 -12 缓释微球制备及体外表征

目的:开发一种白细胞介素-12(IL-12)长效缓释微球剂型。方法:采用水包油-油包固(S/O/W)法制备了白介素-12因子多糖微粒的聚乳酸-聚羟基乙酸共聚物(PLGA-PLA)微球,研究了微球的表面形态和粒径大小,并且运用ELISA方法考察了微球的体外释放效果和免疫活性。结果:本方法制备的白介素-12因子微球光滑圆整,体外缓释达45天,累积释放率近90%。结论:本方法制备的白介素-12因子微球,不仅具有有效地保护IL-12蛋白活性,同时实现长效缓释的目标,是一种可行的IL-12缓释方案。     

Preparation of biodegradable microspheres and matrix devices containing naltrexone

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.     

Spray-dried mucoadhesive microspheres: Preparation and transport through nasal cell monolayer

The purpose of this research was to prepare spray-dried mucoadhesive microspheres for nasal delivery. Microspheres composed of hydroxypropyl methylcellulose (H), chitosan (CS), carbopol 934P (CP) and various combinations of these mucoadhesive polymers, and maltodextrin (M), colloidal silicon dioxide (A), and propylene glycol (P) as filler and shaper, were prepared by spray-drying technique. Using propranolol HCl as a model drug, microspheres were prepared at loadings exceedings 80% and yields between 24% and 74%. Bulky, free flowing microspheres that had median particle size between 15 and 23 μm were obtained. Their zeta potential was according to the charge of polymer. Adhesion time of mucoadhesive microspheres on isolated pig intestine was ranked, CS>CP: H>CP>H, while the rank order of swelling was CP>CS>H. Increasing the amount of CP in CP∶H formulations increased the percentage of swelling. Infrared (IR) spectra showed no interaction between excipients used except CS with acetic acid. The release of drug from CP and CP∶H microspheres was slower than the release from H and CS microspheres, correlated to their viscosity and swelling. Long lag time from the CP microspheres could be shortened when combined with H. The permeation of drug through nasal cell monolayer corresponded to their release profiles. These microspheres affected the integrity of tight junctions, relative to their swelling and charge of polymer. Cell viability was not affected except from CS microspheres, but recovery could be obtained. In conclusion, spray-dried microspheres of H, CS, CP, and CP∶H could be prepared to deliver drug through nasal cell monolayer via the opening of tight junction without cell damaging. Published: February 10, 2006     

一种白细胞介素-2缓释微球制备新方法及体外表征

目的：开发一种白细胞介素-2（m-2）长效缓释微球剂型。方法：采用S／O／W法制备了白介素-2因子多糖微粒的PLGA微球,考察了微球的表面形态、粒径分布等,并且运用ELISA方法考察了微球的体外释放效果。结果：本方法制备的白介素-2因子微球光滑圆整,粒径分布较均匀,体外缓释达32天,累积释放率近90％。结论：本方法制备的白介素-2因子微球,不仅具有有效地保护IL-2蛋白活性,同时实现长效缓释的目标,是一种可行的蛋白缓释方案。