Microparticles of poly(3-hydroxybutyrate-co-3-hydroxyvalerate)(PHBV) and poly(ε-caprolactone)(PCL) containing resveratrol were successfully prepared by simple emulsion/solvent evaporation. All formulations showed suitable encapsulation efficiency values higher than 80%. PHBV microparticles revealed spherical shape with rough surface and presence of pores. PCL microparticles were spherically shaped with smooth surface. Fourier-transformed infrared spectra demonstrated no chemical bond between resveratrol and polymers. X-ray powder diffraction patterns and differential scanning calorimetry analyses indicated that microencapsulation led to drug amorphization. These PHBV/PCL microparticles delayed the dissolution profile of resveratrol. Release profiles were better fitted to biexponential equation. The hypochlorous-acid-scavenging activity and 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation discoloration assay confirmed that the antioxidant activity of PHBV/PCL microparticles was kept, but was dependent on the microparticle morphology and dissolution profile. Resveratrol-loaded PHBV/PCL microparticles showed no cytotoxic effect on red blood cells.

The aim was to prepare theophylline-loaded Eudragit RS 100 microsphere to achieve sustained release pattern with relatively high production yield. To this end, microspheres were prepared by oil/oil solvent evaporation method using an acetone-methanol mixture and liquid paraffin system containing aluminum tristearate. Drug release profiles were determined at pH 1.2 and 7.4. Morphology and solid state of microspheres were examined using SEM, DSC, X-ray powder diffraction (XRPD), and FT-IR. As the ratio of acetone/methanol increased during the preparation of microspheres the size of microsphere was reduced. The highest drug loading efficiency (87.21%) was obtained for the microsphere containing a high ratio of polymer to drug (6:1) and high volume of acetone. SEM studies showed that the microspheres are almost spherical with a few pores and cracks at surfaces. The FT-IR, XRPD and DSC results ruled out any chemical interaction between theophylline and Eudragit. The microspheres prepared with low ratio of polymer to drug (1:2) showed faster dissolution rate than those with high polymer to drug ratio. The ratio of polymer to drug and the volume of polymer solvent were found to be the key factors affecting the release profile which could lead to microspheres with desired release behavior.

Sodium alendronate is an effective treatment for osteoporosis, but its oral administration is associated with adverse gastrointestinal effects. The aim of this work was to evaluate gastroresistant sodium alendronate-loaded microparticles prepared by spray-drying using Eudragit((R)) S100 or a blend of Eudragit((R)) S100/Methocel((R)) E4M. Both formulations presented high encapsulation efficiencies, mean diameters below 17 mum, and similar collapsed shape. Dissolution experiments showed good gastro-resistance for the microparticles at pH 1.2. At pH 6.8, the blended microparticles retarded the drug release. In vivo studies showed that the formulations were able to protect the rat stomachs against ulcer formation by sodium alendronate. In conclusion, the microparticles seems to be promising oral carriers for sodium alendronate.

Pantoprazole-loaded microparticles were prepared using a blend of Eudragit(R) S100 and Methocel(R) F4M. The accelerated stability was carried out during 6 months at 40 degrees 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.

Pantoprazole is a proton pump inhibitor prodrug used in the treatment of gastric ulcers and gastroesophageal disease. Pantoprazole must be absorbed in the gastrointestinal tract and because it is unstable under acidic conditions, enteric delivery systems are required. The purpose of this study was to prepare pantoprazole-loaded microspheres by emulsion-solvent evaporation technique using two different types of enteric-coating polymers: Eudragit S 100 and hydroxypropyl methylcellulose phtalate. The microspheres have been characterized in terms of their morphology, encapsulation efficiency, and ability of stabilizing pantoprazole in acidic media. Pantoprazole determinations were carried out using a validated spectrophotometric method for the analysis of drug in dissolution media. All microspheres, except F2 formulation, were successfully obtained. The in vitro assay showed that especially F1 and F4 microspheres were more effective in protecting the drug than F3 microspheres in acidic media.

Pantoprazole sodium is a proton pump inhibitor, used in acid-related disorders, like peptic ulcers and gastroesophageal reflux. This drug is unstable in acid solution and in the presence of salts. The aim of this work was to study the photostability under UVC radiation of pantoprazole and to determine its kinetics. A methanol solution and the solid pantoprazole were evaluated by HPLC within 120min and 10 days, respectively. The work was also dedicated to evaluate and compare the ability of microencapsulation in stabilizing pantoprazole after UVC radiation. Pantoprazole-loaded microparticles prepared by emulsification/solvent evaporation or spray drying were compared. Pantoprazole was encapsulated using Eudragit S100((R)) or its blend with poly(epsilon-caprolactone) or HPMC. In methanol solution, pantoprazole was completely degraded after 120min and presented zero-order kinetics with t(1/2) of 6.48min. In the solid form, after 10 days, pantoprazole concentration was reduced to 27% following zero-order kinetic. The microparticles prepared only with Eudragit S100((R)) demonstrated an increase of the drug photostability. After 10 days of irradiation, 56 and 44% of the drug was stable when encapsulated by emulsification/solvent evaporation and spray drying, respectively. The use of polymer blends did not improve the pantoprazole photostability.

Pantoprazole is used in the treatment of acid related disorders and Helicobacter pylori infections. It is activated inside gastric parietal cells binding irreversibly to the H+/K(+)-ATPase. In this way, pantoprazole must be absorbed intact in gastro-intestinal tract, indicating that enteric delivery systems are required. The purpose of this study was to prepare pantoprazole-loaded microparticles by spray-drying using a blend of Eudragit S100 and HPMC, which can provide gastro-resistance and controlled release. Microparticles presented acceptable drug loading (120.4 mgg(-1)), encapsulation efficiency (92.3%), surface area (49.0 m2g(-1)), and particle size (11.3 microm). DSC analyses showed that the drug is molecularly dispersed in the microparticles, and in vivo anti-ulcer evaluation demonstrated that microparticles were effective in protecting stomach against ulceration. Microparticles were successfully tabletted using magnesium stearate. In vitro gastro-resistance study showed that microparticles stabilized pantoprazole in 62.0% and tablets in 97.5% and provided a controlled release of the drug.

The influence of the spray-drying process on the ability of engineered lipid-core nanocapsules to protect tretinoin against UV degradation was evaluated. This approach represents a technological alternative to improve the microbiological stability, storage and transport properties of such formulations. Tretinoin-loaded lipid-core nanocapsules or tretinoin-loaded nanoemulsion were dispersed in lactose (10% w/v) and fed in the spray-drier to obtain a solid product (spray-dried powder containing tretinoin-loaded nanocapsules or nanoemulsion--SD-TTN-NCL or SD-TTN-NE, respectively). SD-TTN-NE showed a lower (p < or = 0.05) percentage of encapsulation (89 +/- 1%) compared to SD-TTN-NCL (94 +/- 2%). Redispersed SD-TTN-NCL and SD-TTN-NE showed z-average sizes of 204 +/- 2 nm and 251 +/- 9 nm, which were close to those of the original suspensions (220 +/- 3 nm and 239 +/- 14 nm, respectively). Similar percentage of photodegradation were determined for tretinoin loaded in nanocapsules (26.15 +/- 4.34%) or in the respective redispersed spray-dried powder (28.73 +/- 6.19 min) after 60 min of UVA radiation exposure (p > 0.05). Our experimental design showed for the first time that spray-dried lipid-core nanocapsules are able to protect tretinoin against UVA radiation, suggesting that the drying process did not alter the supramolecular structure of the lipid-core nanocapsules. Such powders are potential intermediate products for the development of nanomedicines containing tretinoin.

To evaluate the effect of cationic coating of polymeric nanocapsules in sunscreen formulations on the in vitro skin penetration of benzophenone-3. Benzophenone-3-loaded nanocapsules were prepared by the interfacial deposition of poly(ε-caprolactone) and coated by using a chitosan solution. The nanoparticles were characterized and incorporated in hydrogels. The presence of nanoparticles in hydroxyethyl cellulose gels was observed by transmission electron microscopy and photon correlation spectroscopy. Penetration studies were carried out using Franz cells with porcine skin membranes. Benzophenone-3-loaded chitosan-coated nanocapsules presented a mean size of 202 ± 7 nm and positive zeta potential (+21 ± 1 mV), while these values for the uncoated nanocapsules were 175 ± 1 nm and -8 ± 1 mV. Penetration profiles showed that a higher amount of benzophenone-3 remained at the skin surface and a lower amount was found in the receptor compartment after the application of the formulation containing chitosan-coated nanocapsules compared to a formulation containing its free form. Hydrogel containing benzophenone-3 chitosan-coated nanocapsules represents an innovative formulation to overcome limitations of sunscreen daily use.

Non-specific protein adsorption from complex biological media, especially from blood plasma, is an urgent challenge for the application of nanoparticles as delivery systems, diagnostics, and other biomedical application. Nanocapsules (NC) prepared from FDA-approved degradable poly(ɛ-caprolactone) shell and Mygliol 812(®) oil in the core were coated with mono-methoxy terminated oligo(ethylene glycol) methacrylate (poly(MeOEGMA)) polymer brush layers with a well-controlled thickness at the nanometer scale up to 350 nm using surface initiated atom transfer radical polymerization in water or phosphate buffered saline. Incubation of uncoated NC with human serum albumin solution, fetal bovine serum, or human blood plasma resulted in fast aggregation observed by dynamic light scattering as an increase in diameter of particles present in the solutions. Conversely, these biological fluids affected only marginally the size distribution of the NC coated with a 60 nm thick poly(MeOEGMA) layer. The high suspension stability of the coated NC in complex biological fluids was related to the suppressed deposition of proteins from these fluids observed by surface plasmon resonance (SPR) on analogous poly(MeOEGMA) layer prepared on flat surfaces of SPR chips.

The influence of the polymeric amorphous materials on the physicochemical and drug release properties of drug-loaded nanocapsules as well as their role on the protection of the entrapped drug against the degradation induced by UV radiation was evaluated. Nanocapsules were prepared by interfacial deposition of preformed polymer (PLA, PLGA 50:50, and PLGA 85:15) using clobetasol propionate as the drug model. In vitro drug release was evaluated by the dialysis bag method. Photochemical stability was studied under UVA radiation. After preparation, all formulations presented nanometric mean size (180-200 nm), polydispersity index below 0.20, acid pH, negative zeta potential, and encapsulation efficiency close to 100%. Clobetasol propionate-loaded PLGA nanocapsules presented a lower physicochemical stability, showing a high drug leakage during 3 months of storage. In vitro studies showed biphasic drug release from all nanocapsules (according to an anomalous transport) and no influence of the hydrophilic characteristics of the amorphous polymeric material on the release rate. The photostability of clobetasol propionate under UVA radiation was improved by its incorporation into PLA and PLGA nanocapsules showing that besides semicrystalline polymers, amorphous polymers could also efficiently protect nanoencapsulated drugs against UV radiation.

The industrial development of polymeric nanoparticle suspensions is still limited due to their low physicochemical stability. In this paper, we evaluated the wet granulation process as an alternative method to dry polymeric nanocapsules using dexamethasone as drug model. Nanocapsule suspensions were used as granulating liquid as well as a drug-loaded-nanocarrier in the wet granulation process. Granules were evaluated regarding their drug content, mean particle size, yield, moisture content, flow properties, stability on storage, recovery studies after water redispersion and morphological characteristics (SEM). Granules containing dexamethasone-loaded polymeric nanocapsules presented good drug content (approximately 94%) and were stable for 6 months at room temperature. Morphological analyses showed nanostructures on their surface and the nanoparticles were recovered after redispersing the granules in water. These results suggest that wet granulation can be an interesting alternative to dry drug-loaded nanocapsule suspensions.

The aim of this study was to prepare and to evaluate the physicochemical and in vitro drug release characteristics of different nanostructured systems containing clobetasol propionate (CP): CP-loaded polymeric nanoparticles (nanocapsules and nanospheres) and CP-loaded nanoemulsion. Physicochemical characteristics of the formulations were monitored up to 9 months after preparation by means of drug content, encapsulation efficiency, mean size, polydispersity index, pH, and zeta potential. In vitro drug release studies were carried out using the dialysis bag method. Photostability of CP-loaded nanoparticles was evaluated by their exposition to UVA radiation. All formulations presented nanometric mean size (140-220 nm), polydispersity index below 0.25, neutral pH values, negative zeta potential and encapsulation efficiency close to 100%. All these parameters, except pH, remained unchangeable up to 9 months of storage at room temperature for CP-loaded nanocapsules. On the other hand, CP-loaded nanospheres and nanoemulsion showed an increase in their mean size, as well as in polydispersity index under storage (after 3 and 6 months, respectively). In vitro drug release studies showed a controlled release of CP from nanoparticles (nanocapsules > nanospheres > nanoemulsion) with a low burst release. Photostability of CP under UVA radiation was improved by its incorporation into nanoparticles (nanocapsules > nanoemulsions > nanospheres).

Background and purpose: The effects of systemic treatment with indomethacin-loaded nanocapsules (IndOH-NC) were compared with those of free indomethacin (IndOH) in rat models of acute and chronic oedema. Experimental approach: The following models of inflammation were employed: carrageenan-induced acute oedema (measured between 30 min and 4 h), sub-chronic oedema induced by complete Freund's adjuvant (CFA)(determined between 2 h and 72 h), and CFA-induced arthritis (oedema measured between 14 and 21 days). Key results: IndOH or IndOH-NC produced equal inhibition of carrageenan-elicited oedema. However, IndOH-NC was more effective in both the sub-chronic (33 +/- 4% inhibition) and the arthritis (35 +/- 2% inhibition) model of oedema evoked by CFA, when compared with IndOH (21 +/- 2% and 14 +/- 3% inhibition respectively)(P < 0.01). In the CFA arthritis model, treatment with IndOH-NC markedly inhibited the serum levels of the pro-inflammatory cytokines tumour necrosis factor alpha and IL-6 (by 83 +/- 8% and 84 +/- 11% respectively), while the levels of the anti-inflammatory cytokine IL-10 were significantly increased (196 +/- 55%). The indices of gastrointestinal damage in IndOH-NC-treated animals were significantly less that those after IndOH treatment (58 +/- 16%, 72 +/- 6% and 69 +/- 2%, for duodenum, jejunum and ileum respectively). Conclusions and implications: IndOH-NC produced an increased anti-inflammatory efficacy in long-term models of inflammation, allied to an improved gastrointestinal safety. This formulation might represent a promising alternative for treating chronic inflammatory diseases, with reduced undesirable effects.

The aim of this study was to prepare and characterize tretinoin-loaded nanocapsules as well as to evaluate the influence of this nanoencapsulation on tretinoin photostability. Tretinoin-loaded nanocapsules (0.5mgml(-1)) were prepared by interfacial deposition of preformed polymer (poly-varepsilon-caprolactone) using two different oily phases: capric/caprylic triglycerides and sunflower seed oil. Tretinoin-loaded nanocapsules presented drug content close to the theoretical value, encapsulation efficiencies higher than 99.9%, nanometric mean size with a polydispersity index below 0.25, and pH values between 5.0 and 7.0. Regarding photodegradation studies, tretinoin methanolic solution showed a half-life time around 40min according to a first order equation, whereas tretinoin nanocapsule suspensions showed a half-life between 85 and 100min (twofold higher than in methanolic solution) according to a zero order equation. Tretinoin-loaded nanocapsules improved tretinoin photostability, independently on the type of oily phase used in this study, and represent a potential system to be incorporated in topical or systemic dosage forms containing tretinoin.

To avoid the clinical inconvenience of repeated injection of the immune modulator thymopentin (TP5), biodegradable implants comprising a mixed polymer matrix of poly(lactide acid)(PLA) and poly(lactide-co-glycolide acid)(PLGA) were produced using a simple extrusion method. Drug release from these TP5-loaded implants was characterized both in vitro and in vivo. Pharmacodynamic studies were carried out in immunosuppressed rats using the ratio of CD4(+)/CD8(+) cells, determined by flow cytometry, as an index of immunity. The results indicated that the entrapment efficiency of the implants was greater than 98%, but the release rate of TP5 depended on the drug loading. Implants containing less than 10% TP5 showed consistent release over 30 days, with low burst-release both in vitro and in vivo. Improved immunity and survival rates were observed in rats treated by TP5 injection and in rats given middle-to-high dose implants. When the release of TP5 exceeded 0.1 mg/kg body weight/day the CD4(+)/CD8(+) ratios increased in the 3 weeks after implantation, reaching a maximum (91.6% of the normal level) by the end of the third week. The TP5-loaded implants presented here provide a promising alternative to injections and the results support the further development of controlled-release TP5 formulations.

A biphasic gastroretentive drug delivery system of fenoverine was developed to maintain constant plasma concentration. The delivery system consisted of a loading-dose tablet and a floating multiple matrix tablet prepared by the direct compression process. The drug release from biphasic GRDDS in 0.1 mol L(-1) HCl and SGF (enzyme free) was sustained over 12 h with buoyant properties. Stability studies showed no significant change in dissolution profiles (f2 value > 50). Based on the release kinetics, it can be concluded that the floating multiple matrix tablet containing HPMC was a particularly suitable gastroretentive drug delivery system with a zero-order release profile.

Sodium alendronate is an effective treatment for osteoporosis, but its oral administration is associated with adverse gastrointestinal effects. The aim of this work was to evaluate gastroresistant sodium alendronate-loaded microparticles prepared by spray-drying using Eudragit((R)) S100 or a blend of Eudragit((R)) S100/Methocel((R)) E4M. Both formulations presented high encapsulation efficiencies, mean diameters below 17 mum, and similar collapsed shape. Dissolution experiments showed good gastro-resistance for the microparticles at pH 1.2. At pH 6.8, the blended microparticles retarded the drug release. In vivo studies showed that the formulations were able to protect the rat stomachs against ulcer formation by sodium alendronate. In conclusion, the microparticles seems to be promising oral carriers for sodium alendronate.

AIM The aim of this study was to prepare insulin-loaded poly(lactic acid)-polyethylene glycol microspheres that could control insulin release at least for 1 week and evaluate their in vivo performance in a streptozotocin-induced diabetic rat model. METHODS The microspheres were prepared using a water-in-oil-in-water double emulsion solvent evaporation technique. Different formulation variables influencing the yield, particle size, entrapment efficiency, and in vitro release profiles were investigated. The pharmacokinetic study of optimized formulation was performed with single dose in comparison with multiple dose of Humulin 30/70 as a reference product in streptozotocin-induced diabetic rats. RESULTS The optimized formulation of insulin microspheres was nonporous, smooth-surfaced, and spherical in structure under scanning electron microscope with a mean particle size of 3.07 microm and entrapment efficiency of 42.74% of the theoretical amount incorporated. The in vitro insulin release profiles was characterized by a bimodal behavior with an initial burst release because of the insulin adsorbed on the microsphere surface, followed by slower and continuous release corresponding to the insulin entrapped in polymer matrix. CONCLUSIONS The optimized formulation and reference were comparable in the extent of absorption. Consequently, these microspheres can be proposed as new controlled parenteral delivery system.

Acrylic enteric microparticles for oral drug delivery were prepared by an oil-in-oil emulsion solvent evaporation process. The novel use of sorbitan sesquioleate as a surfactant produced Eudragit L55, L and S (pH thresholds of 5.5, 6 and 7, respectively) microparticles of good morphology (spherical, smooth surfaced), size (<100microm) and size uniformity. The process was efficient (yield approximately 90%) and the encapsulated model drug (prednisolone) was in the amorphous form. The Eudragit L and S microparticles showed excellent pH-responsive drug release in dissolution studies (negligible drug release at pH 1.2; rapid drug release above the polymers' pH thresholds). In contrast, Eudragit L55 particles aggregated in fluid and showed poor control of drug release. In vivo in rats, Eudragit L microparticles released their drug load rapidly (T(max)<1h) and the C(max) and AUC were higher than those of a control suspension of prednisolone. Drug absorption from Eudragit S microparticles was low which was attributed to the fact that the threshold pH of Eudragit S was not reached in the rat intestine and drug release was therefore incomplete. It was concluded that although the rat is an inappropriate model for the investigation of Eudragit S microparticles, the positive results seen with the Eudragit L microparticles indicate its potential use in pH-targeted drug delivery.

Aim: The aim of this study was to prepare insulin-loaded poly(lactic acid)-polyethylene glycol microspheres that could control insulin release at least for 1 week and evaluate their in vivo performance in a streptozotocin-induced diabetic rat model. Methods: The microspheres were prepared using a water-in-oil-in-water double emulsion solvent evaporation technique. Different formulation variables influencing the yield, particle size, entrapment efficiency, and in vitro release profiles were investigated. The pharmacokinetic study of optimized formulation was performed with single dose in comparison with multiple dose of Humulin(R) 30/70 as a reference product in streptozotocin-induced diabetic rats. Results: The optimized formulation of insulin microspheres was nonporous, smooth-surfaced, and spherical in structure under scanning electron microscope with a mean particle size of 3.07 mum and entrapment efficiency of 42.74% of the theoretical amount incorporated. The in vitro insulin release profiles was characterized by a bimodal behavior with an initial burst release because of the insulin adsorbed on the microsphere surface, followed by slower and continuous release corresponding to the insulin entrapped in polymer matrix. Conclusions: The optimized formulation and reference were comparable in the extent of absorption. Consequently, these microspheres can be proposed as new controlled parenteral delivery system.

The release of verapamil hydrochloride from tablets with Eudragit RLPO or Kollidon SR with different drug-to-polymer ratios were investigated with a view to develop twice-daily sustained-release dosage form by solid dispersion (SD) technique. The SDs containing Eudragit RLPO or Kollidon SR at drug-polymer ratios of 1:1, 1:2, and 1:3 with verapamil hydrochloride were developed using solvent evaporation technique. The physical mixtures of drug and both polymers were prepared by using simple mixing technique at the same ratio as solid dispersion. The physicochemical properties of solid dispersion were evaluated by using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). The study of DSC, XRD, and FTIR could not show significant interaction between verapamil HCl and Kollidon SR or Eudragit RLPO. The solid dispersions or physical mixtures were compressed to tablets. The tablets were prepared with solid dispersions containing Eudragit RLPO or Kollidon SR, with all the official requirements of tablet dosage forms fulfilled. Tablets prepared were evaluated for the release of verapamil hydrochloride over a period of 12 h in pH 6.8 phosphate buffer using US Pharmacopoeia type II dissolution apparatus. The in vitro drug release study revealed that the tablet containing Eudragit has extended the release rate for 12 h whereas the tablet containing Kollidon SR at the same concentration has extended the release rate up to 8 h. The in vitro release profile and the mathematical models indicate that release of verapamil hydrochloride can be effectively controlled from a tablet containing solid dispersions of Eudragit RLPO. The reduction of size fraction of the SD system from 200-250 to 75-125 microm had a great effect on the drug release.

The purpose was to investigate the effectiveness of an ethylcellulose (EC) bead matrix and different film-coating polymers in delaying drug release from compacted multiparticulate systems. Formulations containing theophylline or cimetidine granulated with Eudragit RS 30D were developed and beads were produced by extrusion-spheronization. Drug beads were coated using 15% wt/wt Surelease or Eudragit NE 30D and were evaluated for true density, particle size, and sphericity. Lipid-based placebo beads and drug beads were blended together and compacted on an instrumented Stokes B2 rotary tablet press. Although placebo beads were significantly less spherical, their true density of 1.21 g/cm(3) and size of 855 mum were quite close to Surelease-coated drug beads. Curing improved the crushing strength and friability values for theophylline tablets containing Surelease-coated beads; 5.7 +/- 1.0 kP and 0.26 +/- 0.07%, respectively. Dissolution profiles showed that the EC matrix only provided 3 h of drug release. Although tablets containing Surelease-coated theophylline beads released drug fastest overall (t(44.2%)= 8 h), profiles showed that coating damage was still minimal. Size and density differences indicated a minimal segregation potential during tableting for blends containing Surelease-coated drug beads. Although modified release profiles >8 h were achievable in tablets for both drugs using either coating polymer, Surelease-coated theophylline beads released drug fastest overall. This is likely because of the increased solubility of theophylline and the intrinsic properties of the Surelease films. Furthermore, the lipid-based placebos served as effective cushioning agents by protecting coating integrity of drug beads under a number of different conditions while tableting.

Chitosan treated alginate microparticles were prepared with the purpose of incorporating all-trans retinoic acid (ATRA) using an inexpensive, simple and fast method, enhancing dermal localization and sustaining the release of ATRA into the skin. Microparticles characterization, drug-polymer interaction, release profile and in vitro skin retention were investigated. Microparticles presented spherical shape and drug loading capacity of 47%. The drug content of these microparticles was affected by ATRA concentration and by the solvent used and it was more weakly affected by chitosan concentration. The release of ATRA was also affected by chitosan concentration. Microparticles prepared with 0.4% chitosan (w/w) resulted in drug release with a more sustained profile. The results of in vitro retention studies showed that chitosan treated alginate microparticles decreased the drug retention in the stratum corneum (SC), where occur the skin irritation, but maintained the ATRA concentration in the deeper skin layers, where occur the pathologies treated with ATRA. Then, the microparticles developed in this work can be a good candidate to improve the topical therapy with retinoid.

The objective of this study is to select a multiple-unit sustained-release formulation and to compare it with both commercial immediate and single unit sustained-release capsules and also to determine whether an in vitro-in vivo correlation exists for single- and multiple- unit formulations. Indomethacin (20-60% w/w)-loaded, multiple-unit polystyrene microparticles were prepared by emulsion-solvent evaporation method from an aqueous system. The in vitro release profiles obtained in phosphate buffer of pH 6.8 for drug-loaded polystyrene microparticles and for commercial sustained-release capsules (Indocap-SR, 75 mg) were compared. As the microparticles with 50% indomethacin load showed a release profile comparable to that of the Indocap-SR release profile, the microparticles with this drug load was considered as optimized/selected formulation and, therefore, was subjected to stability study and in vivo study in human volunteers. In spite of significantly higher C(max), Ka, and Ke, and lower T(max), t1/2a, t1/2e and AUC(0 --> infinity)) values observed with commercial Microcid immediate-release capsules, there was no sign of difference among the listed parameters between optimized microparticles and Indocap-SR capsules. Indeed, the values of retard quotient (Rdelta) calculated from half-value duration analysis did not show any statistical difference, indicating the occurrence of an almost same degree of retardation of drug release from the optimized microparticles and the Indocap-SR capsules. Furthermore, linear relationship obtained between the percentages dissolved and absorbed suggests a means to predict in vivo absorption by measuring in vitro dissolution. The results suggest that the optimized polystyrene microparticles could provide an alternative controlled-release drug delivery system for indomethacin.