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Herein, a sensitive and selective gas chromatography-electron capture detector (GC-ECD) method was developed and validated for the quantification of trace levels of five bromo-containing genotoxic impurities in Febuxostat active pharmaceutical ingredient (API) after headspace sampling (HS). Multivariate experimental designs for the optimization of static headspace parameters were conducted in two stages using fractional factorial design (FFD) and central composite design (CCD). The optimum headspace conditions were 5 min of extraction time and a 120 °C extraction temperature. Baseline separation on the analytes against halogenated solvents was carried out using an Agilent DB-624 (30 m × 0.32 mm I.D., 1.8 μm film thickness) stationary phase under isothermal conditions. The method was validated according to ICH guidelines in terms of specificity, linearity, the limits of detection and quantification, precision and accuracy. The linearity was assessed in the range of 5–150% with respect to the specification limit. The achieved LOD and LOQ values ranged between 0.003 and 0.009 and 0.01 and 0.03 μg mL−1, respectively. The accuracy of the method (expressed as relative recovery) was in the range of 81.5–118.2%, while the precision (repeatability, inter-day) was less than 9.9% in all cases. The validated analytical protocol has been successfully applied to the determination of the impurities in various Febuxostat API batch samples. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to use commercial available polymers like PVP/PEG, soluplus® and kollidon® SR to prepare immediate and sustained release formulations of felodipine by hot melt mixing method. Solid dispersions containing 5, 10, 20 and 30 wt% drug have been prepared in a Haake-Buchler Reomixer at melt temperature 130 °C and mixing time 10 min. As was found from DSC and XDR studies completely amorphous and miscible solid dispersions can be prepared. In all cases a single glass transition was recorded, which is depended from the used drug amount. Hydrogen bonds and the molecular interaction between felodipine and polymer matrices are responsible for the miscibility of prepared formulations. This has as result the substantial enhancement of felodipine release rate in PVP/PEG mixture and due to the high solubility of used polymers immediate release formulations have been prepared. On the contrary, sustained release formulations can be prepared in the case of kollidon SR solid dispersions. The release mechanism of all preparations was studied using different kinetic models. Finally, binding affinity values calculated by molecular docking simulations were used as estimators for predicting long-term drug's physical stability in solid dispersions. [ABSTRACT FROM AUTHOR]

Abstract: In the present study, ι- and λ-carrageenans were used as appropriate carriers for sustained release formulations of fluvastatin drug. From viscosity measurements, it was found that both carrageenans can give miscible blends with fluvastatin due to the interactions between the sulfate groups of carrageenans and hydroxyl groups of fluvastatin. This was predicted by computational analysis using density functional theory and proved by FTIR spectroscopy. These interactions, which are in higher intensity using ι-carrageenan, lead to the formation of complexes between polymeric matrices and fluvastatin drug. DSC experiments also confirmed that miscible blends between carrageenans and fluvastatin can be formed since in all concentrations only one glass transition temperature was recorded. Fluvastatin release depends on the drug content and in all formulations of λ-carrageenans containing 10, 25 and 50wt% drug, almost sustained release profiles were observed. Fluvastatin/carrageenan complexes have lower dissolution profiles compared with physical mixtures. Polymer swelling seems to be the dominant drug release mechanism. Besides to neat ι- and λ-carrageenans, their blends can be also used as effective matrices for sustained release. [Copyright &y& Elsevier]

Abstract: Polymeric matrices of ι-, κ- and λ-carrageenans and ι-, κ- and λ-carrageenans blends, prepared by simple mixing and by solvent evaporation technique, have been tested for controlled release delivery of Tolterodine l-Tartrate. X-ray diffraction (XRD), infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and viscometry measurements showed that although all weight ratios of carrageenans blends were immiscible, carrageenans formed complexes with the drug through hydrogen bonding. In solid dispersions formulations although the drug was almost immediately dissolved (due to its amorphous character), an amount remained absorbed into polymer matrix and was not released, probably due to hydrogen bonding. When physical mixtures of pure carrageenans and Tolterodine l-Tartrate were prepared, release rate was slower and when λ-carrageenan was used, an almost controlled release formulation was achieved. However, real controlled release formulations were achieved only when physical mixtures of ι-/λ-carrageenans and Tolterodine were used. Thus, the combination of different types of carrageenans could change the carrier’s behaviour. [Copyright &y& Elsevier]

Abstract: The aim of the present study was to experimentally examine whether poorly water-soluble drugs dispersed in a polymeric matrix exist as amorphous nanodispersions or molecularly dispersed compounds. Felodipine (Felo) dispersed in PVP matrix (solid dispersion) was used as a model drug in this study. Drug/polymer ratios have an impact on the drug average particle size, morphology and dissolution profile while solid dispersions containing up to 50wt% Felo are completely amorphous. SEM, TEM micrographs, and micro-Raman mapping reveal that Felo is dispersed in the form of nanoparticles into the PVP matrix. Due to the high spatial resolution of TEM, it was established that these nanoparticles are not uniform particles, but rather agglomerates of individual particles with sizes smaller than 5–10nm. Moreover, micro-Raman mapping allowed us to observe the size and spatial distribution of domains where the drug existed as molecularly or nanodispersed. Experimental evidence presented in this work contradicts the common belief that amorphous poorly water-soluble drugs exist only in the state of molecular dispersion inside a polymer matrix by showing that both types of dispersions (molecular-level and nanodispersions) can coexist. [Copyright &y& Elsevier]

Abstract: In the present study the release mechanism of the sparingly water-soluble drug felodipine (FELO) from particulate solid dispersions in PVP or PEG was investigated. FT-IR data indicated that a N–H⋯O hydrogen bond is formed between FELO and polymers. The drug–polymer interaction was theoretically studied with the density functional theory with the B3LYP exchange correlation function. The interaction energies have been estimated at −31.8kJ/mol for PVP and −18.8kJ/mol for PEG. Also, detailed vibrational analysis of the complexes showed that the red shift of the N–H bond stretching in FELO molecule due to H-bonding was higher in the FELO–PVP complex than in the FELO–PEG complex. Both the experimental and theoretical data indicated that a stronger interaction of FELO with PVP than with PEG was developed. The interactions of FELO with the polymer appeared to control the physical state (amorphous or crystalline) and the particle size of FELO in the solid dispersions. In the FELO/PVP dispersions, the drug is found as amorphous nanoparticles whereas in FELO/PEG dispersions the drug is dispersed as crystalline microparticles. The size of drug particles in the dispersion was also influenced by drug proportion, with an increase in drug content of the dispersion resulting in increased drug particle size. The particle size of drug, the proportion of drug in the dispersion and the properties of the polymer (molecular weight) appeared to determine the mechanism of drug release from the solid dispersions, which was drug diffusion (through the polymer layer)-controlled at low drug contents and drug dissolution-controlled at high drug contents. In situ DLS measurements indicate that the large initial particles of FELO/PVP and FELO/PEG solid dispersions with low drug content (10–20wt%) are very rapidly decreased to smaller particles (including nanoparticles) during dissolution, leading to the observed impressive enhancement of FELO release rate from these dispersions. [Copyright &y& Elsevier]

Abstract: The aim of the present study was to prepare pulsatile release formulations consisting of two-layered tablets appropriate for preventing ischemic heart diseases. For this reason the active core was constituted by a FELO/PVP 10/90 w/w solid dispersion while for the adjustment of the drug release time the coating layer was composed of PVP/HPMC blends at different compositions, acting as a stimulus responsible layer. These blends as was found by DSC studies are miscible in the entire composition range, ensured by the interactions taking place between hydroxyl groups of HPMC and carbonyl groups of PVP. The miscibility of the system enhances the mucoadhesive properties of the blends, compared with those of pure HPMC, which is desired for such applications. The enhancement was attributed to the higher rate of wetting and flexibility of the new matrices due to the faster dissolution of the PVP macromolecules. Upon exposure of the prepared tablets to the release medium it was found that the coating layer disintegrates first, followed by the immediate release of FELO from the active core. The delaying time is based on a complicated mechanism, which is a combination of swelling and erosion of the PVP/HPMC polymer blends. Varying the PVP/HPMC blend ratios, the exact time that FELO is released during a daytime can be effectively adjusted and this ability is expressed mathematically by the equation t =0.028 C 1.5, where C is the concentration of HPMC in the blend. [Copyright &y& Elsevier]

Abstract: Solid dispersion systems are widely investigated for the dissolution enhancement of poorly water soluble drugs. Nevertheless, very limited commercial use has been achieved due to the poor predictability of such systems caused by the lack of a basic understanding of the dissolution optimization mechanism. In the present study an investigation of the release mechanism is performed for solid dispersion systems composed by polyvinylpyrrolidone (PVP) and felodipine (FEL), based on a correlation of their hydrophilicity with the intensity of interactions. The existing interactions were evaluated by using NMR and UV spectroscopy while molecular simulation techniques were also enabled. It was found that the interactions that take place correspond to the creation of hydrogen bonds. The correlation between the intensity of interactions and the concentration of PVP in the matrix showed a sigmoid function. The interactions are impressively increased for polymer concentration exceeding 75% (w/w). This phenomenon was well explained by using the molecular simulation technique. A similar sigmoid pattern was found for the function between dissolution profiles and polymer concentration in the matrix, indicating that the intensity of interactions promotes the dissolution enhancement. Investigation of the solubility and the particle size distribution of FEL in the binary system appeared to have similar behaviour indicating that the interactions affect the release profile through these two factors. The hydrophilicity of PVP does not significantly affect this enhancement as the contact angle was found to be linear to PVP concentration. Microscopic observation of the dissolution behaviour showed that FEL remains in fine dispersion in aqueous solution, verifying the release mechanism. [Copyright &y& Elsevier]

Abstract: In the present study predictable pulsatile chronotherapeutics of felodipine (FELO), which is a poorly-water soluble drug, were prepared in the form of two layered tablets. As active core PVP/FELO nanodispersion was used while as effective coating layer different PVP/HPMC blends were added. From dissolution studies of FELO nanodispersions it was revealed that PVP/FELO 90/10w/w dispersion is an ideal system for pulsatile formulations since the whole amount of FELO is released within the first 30min. This dissolution enhancement and fast release was attributed to FELO amorphisation, as was found from XRD and DMTA techniques and the effective particle size reduction. Transmission electron microscopy (TEM) studies revealed that FELO creates amorphous nanodispersions into the PVP matrix while particle sizes are directly dependable upon FELO concentration. Drug particles with sizes lower than 150nm may be the optimal level for a substantial enhancement of FELO dissolution rate. The time of FELO release initiated by the two-layered tablets was adequately adjusted by using different PVP/HPMC blends as coating layer, which is a swellable and erodible barrier. The delaying time of FELO release is directly depended by HPMC concentration and this correlation was mathematically expressed. The significance of these blends is that they are completely miscible over the entire compositional range, thus forming a new matrix with different physicochemical properties, contrary to the initial polymers. [Copyright &y& Elsevier]

Current transdermal drug delivery technologies, like patches and ointments, effectively deliver low molecular weight drugs through the skin. However, delivering larger, hydrophilic drugs and macromolecules remains a challenge. In the present study, we developed novel transdermal nanoneedle patches containing levofloxacin-loaded modified chitosan nanoparticles. Chitosan was chemically modified with transcutol in three ratios (1/1, 1/2, 1/3, w/w), and the optimum ratio was used for nanoparticle fabrication via the ionic gelation method. The successful modification was confirmed using ATR-FTIR spectroscopy, while DLS results revealed that only the 1/3 ratio afforded suitably sized particles of 220 nm. After drug encapsulation, the particle size increased to 435 nm, and the final formulations were examined via XRD and an in vitro dissolution test, which suggested that the nanoparticles reach 60% release in a monophasic pattern at 380 h. We then prepared transdermal patches with pyramidal geometry nanoneedles using different poly(lactic acid)/poly(ethylene adipate) (PLA/PEAd) polymer blends of varying ratios, which were characterized in terms of morphology and mechanical compressive strength. The 90/10 blend exhibited the best mechanical properties and was selected for further testing. Ex vivo permeation studies proved that the nanoneedle patches containing drug-loaded nanoparticles achieved the highest levofloxacin permeation (88.1%). [ABSTRACT FROM AUTHOR]

Nanocarriers, due to their unique features, are of increased interest among researchers working with pharmaceutical formulations. Polymeric nanoparticles and nanocapsules, involving non-toxic biodegradable polymers, liposomes, solid lipid nanoparticles, and inorganic-organic nanomaterials, are among the most used carriers for drugs for a broad spectrum of targeted diseases. In fact, oral, injectable, transdermal-dermal and ocular formulations mainly consist of the aforementioned nanomaterials demonstrating promising characteristics such as long circulation, specific targeting, high drug loading capacity, enhanced intracellular penetration, and so on. Over the last decade, huge advances in the development of novel, safer and less toxic nanocarriers with amended properties have been made. In addition, multifunctional nanocarriers combining chemical substances, vitamins and peptides via coupling chemistry, inorganic particles coated by biocompatible materials seem to play a key role considering that functionalization can enhance characteristics such as biocompatibility, targetability, environmental friendliness, and intracellular penetration while also have limited side effects. This review aims to summarize the "state of the art" of drug delivery carriers in nanosize, paying attention to their surface functionalization with ligands and other small or polymeric compounds so as to upgrade active and passive targeting, different release patterns as well as cell targeting and stimuli responsibility. Lastly, future aspects and potential uses of nanoparticulated drug systems are outlined. [ABSTRACT FROM AUTHOR]

In the current work, a series of PCL polyesters with different molecular weights was synthesized and used for the fabrication of nanofibrous patches via electrospinning, as sustained release matrices for leflunomide's active metabolite, teriflunomide (TFL). The electrospinning conditions for each sample were optimized and it was found that only one material with high Mn (71,000) was able to produce structures with distinct fibers devoid of the presence of beads. The successful preparation of the fibers was determined by scanning electron microscopy (SEM).TFL (10, 20 and 30 wt%) in three different concentrations was incorporated into the prepared nanofibers, which were used in in vitro drug release experiments. The drug-loaded nanofibrous formulations were further characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffractometry (XRD).It was found that TFL was incorporated in an amorphous form inside the polymeric nanofibers and that significant molecular interactions were formed between the drug and the polyester. Additionally, in vitro dissolution studies showed that the PCL/TFL-loaded nanofibers exhibit a biphasic release profile, having an initial burst release phase, followed by a sustained release until 250 h. Finally, a kinetic analysis of the obtained profiles revealed that the drug release was directly dependent on the amount TFL incorporated into the nanofibers. [ABSTRACT FROM AUTHOR]

Abstract: The effect of plasticizer’s (PEG) molecular weight (MW) on PVP based solid dispersions (SDs), prepared by melt mixing, was evaluated in the present study using Tibolone as a poorly water soluble model drug. PEGs with MW of 400, 600, and 2000g/mol were tested, and the effect of drug content, time and temperature of melt mixing on the physical state of Tibolone, and the dissolution characteristics from SDs was investigated. PVP blends with PEG400 and PEG600 were completely miscible, while blends were heterogeneous. Furthermore, a single Tg recorded in all samples, indicating that Tibolone was dispersed in a molecular lever (or in the form of nanodispersions), varied with varying PEG’s molecular weight, melt mixing temperature, and drug content, while FTIR analysis indicated significant interactions between Tibolone and PVP/PEG matrices. All prepared solid dispersion showed long-term physical stability (18months in room temperature). The extent of interaction between mixture components was verified using Fox and Gordon–Taylor equations. Artificial neural networks, used to correlate the studied factors with selected dissolution characteristics, showed good prediction ability. [Copyright &y& Elsevier]

Poly(vinyl pyrrolidone) (PVP)/poloxamer-188 blends were used as appropriate carriers for the preparation of solid dispersions by hot melt extrusion using aripiprazole (ARIP) as a poor water-soluble model drug. The physical state of ARIP in solid dispersions and its dissolution characteristics were tested for different drug contents and various PVP-to-poloxamer ratios. From TG analysis it was found that all materials were stable at the tested extrusion temperature conditions (110-120 °C) while amorphous drug dispersions were prepared in all cases, due to the miscibility of the polymer matrix with ARIP drug. Furthermore, hydrogen bonds were identified between ARIP (>N-H) and PVP (>C=O) using FT-IR analysis. Finally, ARIP dissolution rate from SDs was pH dependant and increased as the drug content decreased. [ABSTRACT FROM AUTHOR]

Abstract: In the present study, the efficiency of PVP/PEG200 mixtures as appropriate carries for the preparation of solid dispersions by melt mixing was evaluated. Felodipine (FELO) was used as a poorly water soluble model drug. The effect of several melt mixing parameters, (PVP/PEG ratio, time and temperature of melt mixing, and drug content), on the physical state of FELO and the dissolution characteristics of the dispersions were investigated. DSC, XRD, and SEM analysis revealed that in all cases, amorphous drug nanodispersions were prepared. This was attributed to the increased miscibility of the PVP–FELO system, induced by the presence of PEG200, which acted as plasticizer. FT-IR analysis showed hydrogen bonding between FELO (h name="sbnd" />H) and the PVP carrier (h name="dbnd" />O). The release rate of the drug depends mainly on the drug content and is higher in solid dispersions with low drug content and ratio of carrier to plasticizer (PVP/PEG200). The melt mixing variations (time and temperature of mixing) had lower impact on FELO release rate. Finally, artificial neural networks, used to correlate the examined formulation and process variables of hot melt mixing with dissolution parameters, showed good prediction ability. [Copyright &y& Elsevier]

Abstract: Five polyesters based on 1,3-propanediol or ethylene glycol and an aliphatic dicarboxylic acid were used for the preparation of Ropinirole HCl-loaded nanoparticles. The advantage of the present study is that the used polyesters – as well as poly(lactic acid) (PLA) – have similar degree of crystallinity but different melting points, varying from 46.7 to 166.4°C. Based on polymer toxicity on HUVEC, the biocompatibility of these aliphatic polyesters was found comparable to that of PLA and thus the studied polyesters could be used as drug carriers. Drug encapsulation in polyesters was performed via emulsification/solvent evaporation method. Particle size of drug-loaded nanoparticles was between 140 and 190nm, as measured by light scattering. Drug loading content for all the polyesters varies between 10 and 16% and their entrapment efficiency is relatively high (32–48%). WAXD patterns of nanoparticles show that Ropinirole HCl lies in amorphous state within polymer matrices. Drug release diagrams reveal that the higher percentage of Ropinirole HCl is released during the first 6h after its insertion in the dissolution medium. Fast release rates of the drug are attributed to high hydrophilicity of Ropinirole HCl. Melting point (T m) and glass transition temperature (T g) of the host polymer matrices seem to be important parameters, since higher drug release rates are observed in polyesters with low T m and T g. [ABSTRACT FROM AUTHOR]

Raloxifene HCl is a drug with poor bioavailability and poor water solubility. Furthermore n? pharmaceutically acceptable organic solvent has been reported before to dilute the drug. It was observed that Raloxifene HCl can be diluted in a solvent mixture of acetone/water or ethanol/water. The aim of this study was to use biodegradable polymers in order to prepare Raloxifene HCl nanoparticles. For this purpose a series of novel biodegradable poly(ethylene succinate-co-propylene adipate) P(ESu-co-PAd) polyesters were synthesized following the polycondensation method and further, poly(ethylene succinate) (PESu) and poly(propylene adipate) (PPAd) were used. The prepared polyesters were characterized by intrinsic viscosity measurements, end group analysis, enzymatic hydrolysis, Nuclear Magnetic Resonance Spectroscopy (1 -NMR and 13C-NMR) and Wide-angle X-ray Diffractometry (WAXD). The drug nanoparticles have been prepared by a variation of the co-precipitation method and were studied by Wide-angle X-ray Diffractometry (WAXD), FTIR spectrometry, light scattering size distribution, Scanning Electron Microscopy (SEM) and release behavior measurements. The interactions between the polymers and the drug seem to be limited, so the drug occurs in crystalline form in all nanoparticles. The size of the nanoparticles seems to be in the range of 150-350 nm, depending on the polymer that was used. The drug release depends on the melting point and degree of crystallinity of the polyesters used. An initial high release rate was recorded followed by very slow rates of controlled release. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • New chitosan grafted derivatives have been synthesized. • Miscible blends of derivatives with chitosan have been prepared. • The studied blends have super-hydrophilic and high strength properties. • Blend dressings loaded with chloramphenicol offers a promising solution in wound infections. • All dressing shows significant inhibition zone against bacteria strains. Abstract In the present study polymer blends based on chitosan (CS) and its derivatives with trans-aconitic (t-Acon) acid and another with trimellitic (TRM) anhydride, were prepared for topical wound delivery of chloramphenicol (CHL). FT-IR spectroscopy revealed the successful grafting of t-Acon acid or TRM anhydride into CS macromolecules at molar ratios 1:1 and 1:0.5, while powder X-ray diffraction (XRD) analysis showed that the prepared materials were amorphous. Neat chitosan and its grafted derivatives were mixed in different ratios (25/75, 50/50 and 75/25 w/w) in order to prepare suitable blends. Scanning electron microscopy (SEM) showed that the formed blends after freeze-drying had a sponge-like structure, while thermogravimetric analysis (TGA) verified their thermal stability. All blends are miscible in studied compositions and have extensive swelling and much better mechanical properties than neat CS. In a further step, the obtained porous sponges prepared from CS/CS-derivatives 50/50 w/w were loaded with Chloramphenicol (10, 20 and 30 wt%), a broad-spectrum antibiotic, and the prepared dressings were evaluated in terms of FT-IR, XRD, SEM, and in vitro drug dissolution. An initial burst release followed by a quasi-Fickian diffusion driven sustained release phase was observed while the addition of chloramphenicol gives high antimicrobial properties to all dressings. [ABSTRACT FROM AUTHOR]

In this work, a comparison between two different preparation methods for the improvement of dissolution rate of an antifungal agent is presented. Poly("-caprolactone) (PCL) electrospun fibers and β-cyclodextrin (β-CD) complexes, which were produced via an electrospinning process and an inclusion complexation method, respectively, were addressed for the treatment of fungal infections. Voriconazole (VRCZ) drug was selected as a model drug. PCL nanofibers were characterized on the basis of morphology while phase solubility studies for β-CDs complexes were performed. Various concentrations (5, 10, 15 and 20 wt %) of VRCZ were loaded to PCL fibers and β-CD inclusions to study the in vitro release profile as well as in vitro antifungal activity. The results clearly indicated that all formulations showed an improved VRCZ solubility and can inhibit fungi proliferation. [ABSTRACT FROM AUTHOR]

The aim of the present study was to evaluate the effectiveness of neat chitosan (CS) and its derivatives with succinic anhydride (CSUC) and 2-carboxybenzaldehyde (CBCS) as appropriate nanocarriers for ocular release of timolol maleate (Tim). Drug nanoencapsulation was performed via ionic crosslinking gelation of the used carriers and sodium tripolyphosphate (TPP). Nanoparticles with size ranged from about 190 to 525 nm were prepared and it was found that the formed size was directly depended on the used carrier and their ratios with TPP. For CS derivatives it was found that as the amount of TPP increased, the particle size increased too, while both derivatives proceeded to nanoparticles with smaller size than thath of neat CS. The interactions between carriers and TPP were studied theoretically using all-electron calculations within the framework of density functional theory (DFT). In most of nanoparticles formulations, Tim was entrapped in amorphous form, while the drug entrapment efficiency was higher in CBCS derivative.It was indicated that Tim release rate depended mainly on the used carrier, particle size of prepared nanocarriers and drug loading. From the theoretical release data analysis, it was found that the Tim release was a stagewise procedure with drug diffusion being the dominant release mechanism for each stage. [ABSTRACT FROM AUTHOR]

In the present study a series of biodegradable and biocompatible poly(ε-caprolactone)/poly(propylene glutarate) (PCL/PPGlu) polymer blends were investigated as controlled release carriers of Risperidone drug (RISP), appropriate for transdermal drug delivery. The PCL/PPGlu carriers were prepared in different weight ratios. Miscibility studies of blends were evaluated through differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Hydrolysis studies were performed at 37 °C using a phosphate buffered saline solution. The prepared blends have been used for the preparation of RISP patches via solvent evaporation method, containing 5, 10 and 15 wt% RISP. These formulations were characterized using FT-IR spectroscopy, DSC and WAXD in order to evaluate interactions taking place between polymer matrix and drug, as well as the dispersion and the physical state of the drug inside the polymer matrix. In vitro drug release studies were performed using as dissolution medium phosphate buffered saline simulating body fluids. It was found that in all cases controlled release formulations were obtained, while the RISP release varies due to the properties of the used polymer blend and the different levels of drug loading. Artificial Neural Networks (ANNs) were used for dissolution behaviour modelling showing increased correlation efficacy compared to Multi-Linear-Regression (MLR). [ABSTRACT FROM AUTHOR]

Abstract: Polymeric matrices of chitosan (CS), 2-hydroxyethyl starch (HES) and their blends prepared by solvent evaporation technique, have been tested as sustained release hydrogels of ropinirole drug. X-Ray diffraction (XRD), infrared spectroscopy (FT-IR) and viscometry measurements showed that the two polymers can form miscible blends. This miscibility is owed to formed hydrogen bonds taking place between the reactive groups of CS and HES and one glass transition is recorded in all blends. Neat polymers were used to prepare solid dispersion formulations with ropinirole drug. It was found that drug was released immediately within 15–30min from HES while the release was slower from CS matrix. Completely different were the release rates from ropinirole with physical mixtures using neat polymers and their blends. Due to the different solubility and swelling behaviour of CS and HES the release rates showed a sustained profile from the blends containing high amounts of CS. [Copyright &y& Elsevier]

Abstract: Chitosan (CS) nanoparticles of dorzolamide hydrochloride (Dorzo) and pramipexole hydrochloride (Prami) were prepared by the ionic gelation method and their in vitro properties were studied. The long-term objective is the development of efficient ocular formulations for Dorzo and efficient oral formulations for Prami. The particle size of nanoparticles was affected by the CS/drug ratio whereas it was not affected by the type of drug (Dorzo or Prami). Drug association efficiency to the nanoparticles did not appear to correlate with the drug/CS ratio whereas the loading capacity tended to fall with increasing drug proportion. Based on WAXD data, Dorzo was dispersed in the nanoparticles in crystalline form, probably due to the weak interaction developed between Dorzo and CS/TPP matrix as FT-IR data indicated. In contrast, WAXD and step-scan DSC data indicated that Prami formed a molecular dispersion within the nanoparticles. This was probably due to the potent interactions developed between Prami and CS/TPP matrix, as FT-IR data revealed. The nanoparticles exhibited mucoadhesive properties which diminished with increasing drug content. Sustained in vitro drug release was observed with the Dorzo-loaded CS nanoparticles in PBS (pH 7.4) and with the Prami-loaded CS nanoparticles in simulated intestinal fluid. The results obtained in this study suggest that the Dorzo-loaded CS nanoparticles and the Prami-loaded CS nanoparticles could be further evaluated for the controlled ocular delivery of Dorzo and the controlled oral delivery of Prami, respectively. [Copyright &y& Elsevier]

Abstract: Polyvinylpyrrolidone (PVP) and poly(ethylene glycol) (PEG) solid dispersions with Felodipine or Hesperetin having up to 20wt% drug were prepared using solvent evaporation method. Solid dispersions in comparison with their physical mixtures were studied using differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD), scanning electron microscopy (SEM) and hot stage polarizing light microscopy (HSM). PVP formulations with low drug load proved to be amorphous, since no crystalline Felodipine or Hesperetin drugs were detected using DSC and WAXD. Low and fast heating rates were applied for DSC study, to prevent changes in the samples caused during heating. Similarity between results of WAXD and DSC was also found in the case of physical mixtures, where the drug was in the crystalline state. However, though specific tests showed the high sensitivity of the DSC technique, it was difficult to arrive to reliable results for PEG solid dispersions or physical mixtures with low drug content by DSC, even by high heating rates. Crystalline drug could not be detected by DSC, leading to erroneous conclusions about the physical state of the drug, in contrast to WAXD. On the other hand, HSM proved the presence of small drug particles in the solid dispersions with PEG and the dissolution of the drug in the melt of PEG on heating. In such systems, in which a polymer with low melting point is used as drug carrier, DSC is inappropriate technique and must be used always in combination with HSM. The coupling of WAXD with thermal analysis, allowed complete physicochemical characterization and better understanding which is essential for a first prediction of dissolution characteristics of such formulations. [Copyright &y& Elsevier]

The sustained release of pharmaceutical substances remains the most convenient way of drug delivery. Hence, a great variety of reports can be traced in the open literature associated with drug delivery systems (DDS). Specifically, the use of microparticle systems has received special attention during the past two decades. Polymeric microparticles (MPs) are acknowledged as very prevalent carriers toward an enhanced bio-distribution and bioavailability of both hydrophilic and lipophilic drug substances. Poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA), and their copolymers are among the most frequently used biodegradable polymers for encapsulated drugs. This review describes the current state-of-the-art research in the study of poly(lactic acid)/poly(lactic-co-glycolic acid) microparticles and PLA-copolymers with other aliphatic acids as drug delivery devices for increasing the efficiency of drug delivery, enhancing the release profile, and drug targeting of active pharmaceutical ingredients (API). Potential advances in generics and the constant discovery of therapeutic peptides will hopefully promote the success of microsphere technology. [ABSTRACT FROM AUTHOR]