Hydrophilic gels containing chlorophyllin-loaded liposomes: development and stability evaluation

The aim of this study was to develop and characterize hydrophilic gels containing chlorophyllin(CHL)-loaded liposomes as well as to evaluate their stability. Two different CHL-loaded liposome dispersions using non-hydrogenated and hydrogenated soybean lecithin were prepared, characterized for their particle size, polydispersity index and trapping efficiency and incorporated in Carbopol 940 NF hydrogel. The gels obtained were analyzed for flow properties, pH values and CHL content. The control liposome-free gel was obtained by incorporating the CHL solution in the hydrogel. The stability of the gels was evaluated in terms of rheological properties, pH values and CHL content during 6 months' storage at 20 +/- 2 degrees C. Suitable gel formulations for topical use were obtained revealing shear-thinning plastic flow behaviour without significant thixotropy during the whole period of examination. High yield values of the samples during the whole period indicated a long-term stability of the gel formulations. The gel formulations expressed a mild acid value acceptable for topical preparations. After 6 months' storage the CHL content was highest in the gel containing non-hydrogenated lecithin liposomes, followed by the gel containing hydrogenated lecithin liposomes and liposome-free gel, indicating that the encapsulation of CHL in liposomes led to a greater stability of CHL.     

Semisolid topical formulations containing nimesulide-loaded nanocapsules, nanospheres or nanoemulsion: development and rheological characterization

The objective of this work was to develop and characterize semisolid topical formulations containing nimesulide-loaded nanospheres, nanocapsules or nanoemulsion. The nanoprecipitation and spontaneous emulsification methods were used to prepare the colloidal suspensions and the nanoemulsion. The hydrodynamic diameters were 282 nm for the nanoemulsion, 293 nm for the nanocapsules and 191 nm for the nanospheres containing nimesulide. The encapsulation efficiencies were close to 99% in all cases and pH values ranged between 5.1 and 5.3. Each drug-loaded nanocarrier formulation was incorporated in Carbopol 940 gels. The semisolid dosage forms showed yellowish, glossy and homogeneous aspect after the incorporation of the colloidal suspensions and nanoemulsion. The recovery of nimesulide and the pH values for the gels containing nanoemulsion, nanospheres or nanocapsules remained constant during storage (120 days). For all formulations, the rheograms exhibited a non-Newtonian behavior presenting pseudoplastic characteristics and shear thinning. The rheograms were adjusted to Ostwald's model showing regression coefficients higher than 0.9900. None thixotropic phenomenon was experimentally detected under the test conditions for all formulations.     

Poly-epsilon-caprolactone nanocapsules containing octyl methoxycinnamate: preparation and characterization

This study investigates the different nanocapsules (NCs) made of poly-epsilon-caprolactone (PCL) containing the lipophilic sunscreen Escalol 557 [octyl methoxycinnamate (OMC)] and analyzes the influence of nanoparticle-based systems on light-induced decomposition of the sunscreen agent. The NCs were designed and prepared by the solvent displacement method. Formulation parameters, such as the nature and volume of the organic and aqueous phase and the nature and concentration of the surfactants and polymer, have relevant implications on NC elaboration. We investigated the influence of several technological (stirring speed: 300-800 rpm) and formulation factors [polymer amount, 195-244.5 mg; surfactant, Tween 85 (Polysorbate 85), Montanox 80 (Polysorbate 80), and Synperonic PE/F68 (Poloxamer 188) as stabilizing agents; and volume of the organic phase, 20-30 mL of acetone] on the particle size and the OMC loading capacity of the formulations--encapsulation efficiency and yield. The sizes of NC obtained were in the range of 309 to 1042 nm, the encapsulation efficiencies ranged from 93.82% to 99.97%, and yields of NC encapsulation ranged from 48.12% to 86.28%. Of all the preset experimental conditions, Montanox 80, 30 mL of acetone, 244.5 mg of polymer, and a stirring speed of 350 rpm have been selected as the best in this experimental design study. The experimental conditions selected to obtain OMC-loaded NC of 374 nm resulted in a high entrapment percentage (97.52%) and yield (82.95%). The PCL nanoparticles loaded with OMC were effective in reducing light-induced degradation of the sunscreen agent.     

Tretinoin-loaded nanocapsules: Preparation, physicochemical characterization, and photostability study

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 (0.5 mg ml(-1)) were prepared by interfacial deposition of preformed polymer (poly-epsilon-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 40 min according to a first order equation, whereas tretinoin nanocapsule suspensions showed a half-life between 85 and 100 min (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.     

Polymeric colloidal systems containing ethionamide: preparation and physico-chemical characterization

The association of ethionamide with different colloidal systems was evaluated. Nanocapsules (NC), nanospheres (NS), and nanoemulsions (NE) were prepared by interfacial deposition and spontaneous emulsification techniques. Ethionamide was incorporated before (B) and after (A) preparation of nanoparticles. Ethionamide was assayed by HPLC, the particle size was determined using a Nanosizer, and the zeta potential using a Zetasizer 4. Free ethionamide was determined using a combined ultrafiltration-centrifugation technique. The drug release was determined by direct dilution of the nanoparticle dispersion in phosphate-buffer pH 7. All preparations retained acceptable particle size distribution (+/- 300 nm), except the NE. The zeta potential of all formulations was between -36.6 mV and -46.1 mV. Percentages of ethionamide associated were: NC (B: 62.4%, A: 56.2%), NS (B: 53.0%, A: 43.2%), and NE (B: 38.5%). After 45 days, the percentage of drug association with NC increased (B: 66.8%, A: 60.6%). The release profiles demonstrated that associated ethionamide was more readily released from the NC and NS prepared by procedure A rather than B. The ethionamide amount not released (B) was greater in NS than NC. The drug is mainly adsorbed onto the surface of nanoparticles. However, approximately 10% of ethionamide is encapsulated into NC and 20% entrapped into NS, respectively.     

Spray-dried indomethacin-loaded polyester nanocapsules and nanospheres: development, stability evaluation and nanostructure models

The industrial development of polymeric nanoparticle suspensions, as drug delivery systems, is limited due to the problems in maintaining stability of suspensions. In this work, a spray-drying technique was applied to dry nanocapsule and nanosphere suspensions prepared by nanoprecipitation of polyesters using SiO₂ as adjuvant. Powders obtained from nanocapsules presented stable drug recoveries and morphological characteristics after 5 months. For nanocapsules, nanostructures around 200 nm were observed by scanning electron microscopy (SEM) on the surface of microparticles of SiO₂, whereas for the nanosphere formulation, nanostructures with a reduced diameter (60–90 nm) were observed, despite the particle sizes of each original suspension being similar, when measured by photon correlation spectroscopy (PCS). In order to investigate the morphological aspects of nanocapsule and nanosphere powders, several nanosphere formulations were spray-dried using different concentrations of SiO₂ and a comparative study of the different colloidal systems (nanocapsules, nanospheres, nanoemulsion or nanodispersion) was carried out by PCS. SEM analyses showed that nanostructures with reduced diameter are formed independently of the adjuvant concentration. The dynamic properties of these systems allowed to suggest that the structure of the nanosphere particle (polymer, sorbitan monostearate and polysorbate 80) was a polymeric matrix dispersing the sorbitan monostearate which, when submitted to the spray-drying process in the presence of SiO₂, gave nanostructures presenting diameters around 80 nm covering the microparticles due to the release of lipophilic surfactant from the polymeric matrix.     

外用双氯芬酸钾凝胶治疗局部风湿性疼痛综合征

目的 比较研究双氯芬酸钾凝胶（ＤＰＧ）和双氯芬酸钠凝胶（ＤＳＧ）治疗局部风湿性疼痛综合征的疗效和安全性。方法 试验设计为多中心、随机对照、单盲、平行性的比较研究。试验组 ６０例,１％ＤＰＧ外用,每日３－４次,每次２－４ｇ,日总量不超过２０ｇ,疗程２周;对照组４５例,１％ＤＳＧ外用,使用方法同ＤＰＧ。结果 ２周时ＤＰＧ的总有效率为 ８８％,ＤＳＧ总有效率为８７％,ＤＰＧ组疗效明显高于 ＤＳＧ组（Ｐ＜０．０５）。两药均能显著改善病人的临床症状和体征（Ｐ＜０．０５～０．００１）,两组相比ＤＰＧ对关节肿胀数的改善优于ＤＳＧ组（Ｐ＜０．０５）,对其他各指标的改善两组间差异无显著性（Ｐ＞０．０５）． ＤＰＧ的耐受性良好,无１例病人发生不良反应;ＤＳＧ组的不良反应发生率为２％,两组间差异无显著性（Ｐ＞０．０５）．结论ＤＰＧ治疗局部风湿性疼痛综合征的疗效优于ＤＳＧ,且耐受性好,无明显不良反应。     

Anti-inflammatory activity of gel containing novel elastic niosomes entrapped with diclofenac diethylammonium

The objective of this study was to develop a novel elastic bilayer vesicle entrapped with the non-steroidal anti-inflammatory drug (NSAID), diclofenac diethylammonium (DCFD) for topical use. Eighteen bilayer vesicular formulations composing of DPPC or Tween 61 or Span 60 mixed with cholesterol (at 1:1, 3:7 and 1:1 molar ratios, respectively) and ethanol at 0-25% (v/v), by chloroform film method with sonication were developed. The elastic Tween 61 niosomes which gave no sedimentation, no layer separation, unchanged particle sizes (about 200 nm) were selected to entrap DCFD. The entrapment efficiency of the drug in the conventional and elastic Tween 61 niosomes was 65 and 93%, respectively. At least 87% of DCFD determined by HPLC remained in elastic Tween 61 niosomes when kept at 4, 27 and 45 degrees C for 3 months. The deformability index values of the elastic niosomes were 13.76 and 3.44 times higher than the conventional niosomes entrapped and not entrapped with the drug, respectively, indicating the higher flexibility of the elastic vesicle especially, when entrapped with the drug. Transdermal absorption through excised rat skin was performed by vertical Franz diffusion cell at 32+/-2 degrees C for 6h. Gel containing elastic niosomes exhibited fluxes of DCFD in the stratum corneum (SC), deeper skin layer (viable epidermis and dermis, VED) and receiver chamber at 191.27+/-9.52, 16.97+/-2.77 and 3.76+/-0.54 microg/(cm2 h), whereas the commercial emulgel, containing an equivalent DCFD, gave 60.84+/-13.63, 7.33+/-1.70 and 0.14+/-0.01 microg/(cm2 h), respectively. The in vivo anti-inflammatory activity was evaluated by ethyl phenylpropiolate (EPP)-induced rat ear edema (n=3). DCFD entrapped in the developed elastic niosomes and incorporated in gel gave the same ear edema inhibition percentages of 23.81% at 30 min, but 2 and 9 times more inhibition percentages at 45 and 60 min than the commercial emulgel, respectively. This result has not only demonstrated the enhancement of transdermal absorption through rat skin, but also the in vivo anti-inflammatory effect of DCFD when entrapped in the developed novel elastic Tween 61 niosomes, as well.     

Microparticles containing lemongrass volatile oil: preparation, characterization and thermal stability

Lemongrass volatile oil (LVO) is an important ingredient in cosmetics, presenting antimicrobial properties, in particular antifungal activity, and it is a promising raw material for the development of pharmaceutical products. However, its volatility and susceptibility to degradation are the major drawbacks for the use of Cymbopogon citratus oil in pharmaceutical compounding. Thus, the aim of this work was to develop and to characterize microparticles containing this oil viewing the stabilization of LVO. Two techniques of preparation were evaluated; spray drying and precipitation, and two encapsulation materials, beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) were tested. The microparticles were characterized in terms of content of water, yield, percentage of inclusion, infrared spectroscopy. Morphology was evaluated by scanning electronic microscopy. Studies of stability were also conducted. The content of citral (neral and geranial), major component of the oil, present in microparticles was assayed by a validated HPLC method. The percentage of inclusion of LVO into the microparticles was 56-60% and 26-29% using beta-CD and HP-beta-CD, respectively. The results showed that the use of the beta-CD as encapsulant material was more efficient. Additionally, an increased inclusion of lemongrass oil was observed with the precipitation technique.     

Development and characterization of PLGA nanospheres and nanocapsules containing xanthone and 3-methoxyxanthone.

The aim of the present work was to develop and characterize two different nanosystems, nanospheres and nanocapsules, containing either xanthone (XAN) or 3-methoxyxanthone (3-MeOXAN), with the final goal of improving the delivery of these poorly water-soluble compounds. The xanthones-loaded nanospheres (nanomatrix systems) and nanocapsules (nanoreservoir systems), made of poly(DL-lactide-co-glycolide) (PLGA), were prepared by the solvent displacement technique. The following characteristics of nanoparticle formulations were determined: particle size and morphology, zeta potential, incorporation efficiency, thermal behaviour, in vitro release profiles and physical stability at 4 degrees C. The nanospheres had a mean diameter <170 nm, a narrow size distribution (polydispersity index <0.1), and a negative surface charge (zeta potential <-36 mV). Their incorporation efficiencies were 33% for XAN and 42% for 3-MeOXAN. The presence of the xanthones did not affect the nanospheres size and zeta potential. DSC studies indicated that XAN and 3-MeOXAN were dispersed at a molecular level within the polymeric nanomatrix. Nanocapsules were also nanometric (mean size <300 nm) and exhibited a negative charge (zeta potential <-36 mV). Their incorporation efficiency values (>77%) were higher than those corresponding to nanospheres for both xanthones. The release of 3-MeOXAN from nanocapsules was similar to that observed for the correspondent nanoemulsion, indicating that drug release is mainly governed by its partition between the oil core and the external aqueous medium. In contrast, the release of XAN from nanocapsules was significantly slower than from the nanoemulsion, a behaviour that suggests an interaction of the drug with the polymer. Nanocapsule formulations exhibited good physical stability at 4 degrees C during a 4-month period for XAN and during a 3-month period for 3-MeOXAN.     

Nanocapsules, nanoemulsion and nanodispersion containing melatonin: preparation, characterization and stability evaluation

In a previous work, we have demonstrated that melatonin-loaded polymeric nanoparticles provided an important increase in the antioxidant effect of melatonin against lipid peroxidation. Hence, in this work, the aim was to study the stability of nanocapsules containing melatonin (1.5 mg/mL) prepared by interfacial deposition, using different polymers. For comparison, the stability of the nanoemulsion and nanodispersion was also evaluated. These nanoparticulated systems had diameters between 134 and 325 nm. The associated melatonin concentrations ranged from 29% to 50%, depending on the composition of the nanocarriers. The stability evaluation of formulations was preformed at room temperature and protected from or exposed to the natural light or at 50 degrees C and protected from the light. The stability of the nanocarriers was evaluated in terms of the macroscopic aspects, the total contents of melatonin, associated melatonin concentrations, pH and sizes of particles. The compositions of the nanocarriers and the condition of storage influenced the stability of melatonin.     

Comparative pharmacokinetics and bioavailability study of percutaneous absorption of diclofenac from two topical formulations containing drug as a solution gel or as an emulsion gel.

In a 3-way cross-over study on 12 healthy adult volunteers, the percutaneous absorption of diclofenac (CAS 15307-79-6) was studied for two topical formulations containing 1% diclofenac. The relative bioavailability from the test formulation (a solution gel) in terms of Cmax and AUC, calculated from the amount of drug reaching the systemic circulation, was found to be twice the amount after application of reference product (an emulsion gel). The maximum concentration of the drug, from both topical formulations reaching the blood after cutaneous absorption was less than 10% of that obtained after the parenteral administration, which indirectly is indicative that adverse effects normally related to high drug blood concentrations, such as reached after oral administration, are unlikely to be experienced.     

Effect of sodium chloride on the gelation temperature, gel strength and bioadhesive force of poloxamer gels containing diclofenac sodium

Liquid suppository systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and mucoadhesive to the rectal tissues without leakage after the dose. However, a liquid suppository system containing diclofenac sodium could not be developed using bioadhesive polymers, since the drug was precipitated in this preparation. To develop a liquid suppository system using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers and sodium chloride were investigated. The mixtures of P 407 (15%) and P 188 (15-20%) existed as a liquid at room temperature, but gelled at physiological temperature. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. Furthermore, the poloxamer gels with less than 1.0% of sodium chloride, in which the drug was not precipitated, were inserted into the rectum of rabbits without difficulty and leakage, and retained in the rectum of rats for at least 6 h. Our results suggested that a thermosensitive liquid suppository system with sodium chloride and poloxamers was a more physically stable and convenient rectal dosage form for diclofenac sodium.     

Design,development, physicochemical,and in vitro and in vivo evaluation of transdermal patches containing diclofenac diethylammonium salt

In this study, matrix-type transdermal patches containing diclofenac diethylamine were prepared using different ratios of polyvinylpyrrolidone (PVP) and ethylcellulose (EC) by solvent evaporation technique. The drug matrix film of PVP and EC was casted on a polyvinylalcohol backing membrane. All the prepared formulations were subjected to physical studies (moisture content, moisture uptake, and flatness), in vitro release studies and in vitro skin permeation studies. In vitro permeation studies were performed across cadaver skin using a modified diffusion cell. Variations in drug release profiles among the formulations studied were observed. Based on a physicochemical and in vitro skin permeation study, formulation PA4 (PVP/EC, 1:2) and PA5 (PVP/EC, 1:5) were chosen for further in vivo experiments. The antiinflammatory effect and a sustaining action of diclofenac diethylamine from the two transdermal patches selected were studied by inducing paw edema in rats with 1% w/v carrageenan solution. When the patches were applied half an hour before the subplantar injection of carrageenan in the hind paw of male Wistar rats, it was observed that formulation PA4 produced 100% inhibition of paw edema in rats 12 h after carrageenan insult, whereas in the case of formulation PA5, 4% mean paw edema was obtained half an hour after the carrageenan injection and the value became 19.23% 12 h after the carrageenan insult. The efficacy of transdermal patches was also compared with the marketed Voveran gel and it was found that PA4 transdermal patches produced a better result as compared with the Voveran gel. Hence, it can be reasonably concluded that diclofenac diethylamine can be formulated into the transdermal matrix type patches to sustain its release characteristics and the polymeric composition (PVP/EC, 1:2) was found to be the best choice for manufacturing transdermal patches of diclofenac diethylamine among the formulations studied.     

Formulation and characterization of polyphenol-loaded lipid nanocapsules

The purpose of this study was to design and characterize two flavonoid-loaded lipid nanocapsules (LNC) by applying the phase inversion process, and to enhance their apparent solubility and/or the stability. The flavonoid-loaded LNC were characterized by particle size, encapsulation efficiency, drug leakage rates, stability and spectroscopic studies. It was observed that quercetin-loaded LNC30 (3%) and LNC60 (2%) carried a particle size of 30.3 and 55.1 nm, respectively and significant higher entrapment efficiency. Encapsulation of quercetin (QC) in LNC enabled us to increase its apparent aqueous solubility by a factor of 100. And in view of calculations and results, it seems most probable that QC is arranged at this LNC interface between the oil phase and the hydrophilic polyethylene glycol moieties of the surfactant. In addition, colloidal suspensions proved to be stable in term of encapsulation for at least 10 weeks and QC was not oxidised. With simple chemical modification of (−)-epigallocatechin-3-gallate or (−)-EGCG, it was possible to reach very high encapsulation rates (95%). Thus we obtained stable colloidal suspensions of (−)-EGCG in water over 4 weeks while free (−)-EGCG solubilised in water exhibited 100% degradation within 4 h. The initial problems (solubility and stability) of these flavonoids were resolved thanks to drug-loaded LNC.     

Tamoxifen citrate loaded chitosan-gellan nanocapsules for breast cancer therapy: development,characterisation and in-vitro cell viability study

The objective of this study was to evaluate the potential of chitosan-gellan nanocapsules (CGNCs) for encapsulation and sustained release of Tamoxifen citrate (TMC) for breast cancer therapy. Polyelectrolyte complex coacervation method was used for production of CGNCs. Interaction studies were conducted by Fourier-transform infra-red (FT-IR), differential scanning colorimetric (DSC), and X-ray diffraction (XRD) to investigate any interaction between drug and excipients. Physicochemical parameters, in vitro drug release and release kinetic were studied. In vitro cell viability study using Michigan Cancer Foundation-7 (MCF-7) breast cancer cells was also investigated. CGNCs had a smooth surface and nanosize range with a positive surface charge and exhibited sustained drug release. Further, TMC loaded CGNCs were found to be more cytotoxic than the free drug in MCF-7. Thus CGNCs may be suitable for breast cancer treatment due to delivering the drug at the site of action for a prolonged period of time.     

Spray-dried microparticles containing polymeric nanocapsules: formulation aspects, liquid phase interactions and particles characteristics

Up to now, the full potential of polymer-based nanoparticles is not yet exploited because of a lack of stability when conserved in aqueous medium. The present paper reports the water elimination from nanocapsules (NC) dispersions by means of the spray-drying technique with the aim to achieve dried solid forms of interest using colloidal silicon dioxide as drying auxiliary. The influence of formulation parameters on the suspension behaviour and on the powders characteristics was also evaluated. Our findings demonstrated that the mixing protocol, the concentrations of both NC and silica are crucial parameters that affect the feed behaviour and the spray-dried particles characteristics. Interactions occurring in the feed are directed by hydrogen bounds and were more sensitive to the silica concentration than that of NC as evidenced by rheological measurements. The NC are entrapped within solid dried matrixes following their interaction with silica particles in the feed. SEM analyses of the obtained powders showed spherical separated microparticles formed by the association of NC and silica when they are mixed at adequate concentrations in the feed before spray-drying. On the other hand, fused agglomerated particles presenting NC at their surface, characterised by irregular shapes and a strong adhesiveness were prepared when the silica concentration was not sufficient. The surface composition of the spray-dried powders was investigated using the ESCA technique and revealed the NC exclusion from the surface to obtain powders suitable for further handling.     

Physicochemical characterization and in vivo evaluation of poloxamer-based solid suppository containing diclofenac sodium in rats

To develop a poloxamer-based solid suppository with poloxamer mixtures, the melting point of various formulations composed of poloxamer 124 (P 124) and poloxamer 188 (P 188) were investigated. The dissolution and pharmacokinetic study of diclofenac sodium delivered by the poloxamer-based suppository were performed. Furthermore, the identification test in the rectum and morphology test of rectal tissues were carried out after its rectal administration in rats. The poloxamer mixtures composed of P 124 and P 188 were homogeneous phases. Very small amounts of P 188 affected the melting point of poloxamer mixtures. In particular, the poloxamer mixture [P 124/P 188 (97/3%)] with the melting point of about 32 degrees C was a solid form at room temperature and instantly melted at physiological temperature. Very small amounts of P 188 hardly affected the dissolution rates of diclofenac sodium from the suppository. Dissolution mechanism analysis showed the dissolution of diclofenac sodium was proportional to the time. The poloxamer-based suppository gave significantly higher initial plasma concentrations and faster T(max) of diclofenac sodium than did conventional PEG-based suppository, indicating that the drug from poloxamer-based suppository could be absorbed faster than that from PEG-based one in rats. It retained in the rectum for at least 4 h and could not irritate or damage the rectal tissues of rats. Thus, the poloxamer-based solid suppository with P 124 and P 188 was a mucoadhesive, safe and effective rectal dosage form for diclofenac sodium.     

Synthesis, characterization, and biological evaluation of novel diclofenac prodrugs

Diclofenac ester pro drugs (4, 5, 6) were synthesized and evaluated in vitro and in vivo for their potential use for oral delivery, with the aim of obtaining enzymatically labile and less ulceration drugs than the parent drug diclofenac sodium (1a). Prodrugs 4, 5, 6 were found to be potent anti-inflammatory drugs with less ulcerogenic potential than the parent diclofenac sodium. Prodrugs 4, 5, 6 rapidly underwent enzymatic hydrolysis to release the parent drug diclofenac in 30-60 min in rat liver microsomes (RLM) and rat plasma (RP). Prodrugs were found to be more lipophilic when the partition coefficient was measured in 1-octanol and buffer system at pH 7.4 and 3.0. Diclofenac prodrugs 4, 5, 6 were found to be crystalline in nature (analyzed by PXRD). Prodrug 4 was found to be a superior candidate for the treatment of chronic inflammatory diseases.     

Physicochemical and morphological characterization of polyisobutyl cyanoacrylate nanocapsules

Two different polymerization mechanisms of alkyl cyanoacrylates were compared with regard to their morphological and physico-chemical characteristics. Cyanoacrylates were polymerized by simple emulsification into an aqueous medium or by interfacial polymerization in an o/w type emulsion. Suspensions of particles obtained by these two mechanisms show dramatic differences when studied for their turbidity, refractive index, and stability following centrifugation. These observations are consistent with the fact that nanoparticles obtained by emulsion polymerization are known to be formed by a full polymer core, while nanocapsules obtained by interfacial polymerization were thought to consist of an internal oil droplet surrounded by a polymeric wall. This theory was further confirmed by an electron microscopic examination of the internal structures of the two types of polymeric aggregates.