Computational prediction of glass-forming ability and crystallization tendencies

The Third Annual FPTP Network Meetin

Mucoadhesive microspheres of chitosan and polyvinyl alcohol as a carrier for intranasal delivery of insulin: in vitro and in vivo studies

The aim of this study was to investigate the capabilities of chitosan microspheres as drug carrier system in co-formulation with polyvinyl alcohol (PVA), to improve the systemic absorption of intranasal insulin delivery. Insulin loaded microspheres was developed from varying ratio of chitosan solutions along with polyvinyl alcohol (PVA) as additive polymer using spray drying method. Different formulations were developed and morphological studies of the optimized formulas showed that the size range of spherical shaped particulate matters existed from 200 nm to 2 mm. It was clearly observed that physicochemical properties of the microspheres were extensively affected by changing the concentration ratio of the two polymeric materials. In vitro studies of insulin release pattern was performed in various time intervals up to 24 h. It was evident that microspheres made up of chitosan showed initial burst release but slower release as the experiment continued. Microspheres made up of combination of the aforementioned two polymers had instant, sharp and burst drug release. Surprisingly there was no absorption after intranasal delivery of chitosan-PVA microspheres in groups of rats comparing to formulated chitosan microspheres having profound absorption due to their smaller particle size, slower drug release rate and better mucoadhesive properties. Therefore, significant reduction in the plasma blood glucose level for chitosan based optimized formulation was seen right after 4.5 hours compared with control group. The aim of the present study was to fabricate an appropriate application of polymeric microspheres for intranasal delivery of insulin using a novel optimized formulation based on industrial level spray drying technique and to realize the possible barriers in scale up process of its large scale production, considering the effectiveness of polyvinyl alcohol (PVA) and chitosan to increase mucoadhesivness, gelling ability and ultimately effective release behavior pattern of insulin. According to this study, the combination of the polymers used and the mean particle size of formulated microspheres were found to be key factors in insulin drug release resulting for further enhancement of insulin absorption via intranasal route of delivery

Thermodynamic investigation of carbamazepine-saccharin co-crystal polymorphs

YesPolymorphism in active pharmaceutical ingredients (APIs) can be regarded as critical for the potential that crystal form can have on the quality, efficacy and safety of the final drug product. The current contribution aims to characterize thermodynamic interrelationship of a dimorphic co-crystal, FI and FII, involving carbamazepine (CBZ) and saccharin (SAC) molecules. Supramolecular synthesis of CBZ-SAC FI and FII have been performed using thermo-kinetic methods and systematically characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), solubility and slurry measurements. According to Berger and Ramberger’s heat of fusion rule, FI (ΔHfus = 121.1 J/g, mp 172.5 °C) and FII (ΔHfus= 110.3 J/g, mp 164.7 °C) are monotropically related. The solubility and van’t Hoff plot results suggest that FI stable and FII metastable forms. This study reveals that CBZ-SAC co-crystal phases, FI or FII, could be stable to heat induced stresses, however, FII converts to FI during solution mediated transformation.Authors would like to acknowledge UKIERI (TPR 26), EPSRC (EP/J003360/1, EP/L027011/1) for the support. Open Access funded by Engineering and Physical Sciences Research Counci

Polymorphism in sulfadimidine/4- aminosalicylic acid cocrystals: solid-state characterization and physicochemical properties

YesPolymorphism of crystalline drugs is a common phenomenon. However, the number of reported polymorphic cocrystals is very limited. In this work, the synthesis and solid state characterisation of a polymorphic cocrystal composed of sulfadimidine (SD) and 4- aminosalicylic acid (4-ASA) is reported for the first time. By liquid-assisted milling, the SD:4-ASA 1:1 form I cocrystal, the structure of which has been previously reported, was formed. By spray drying, a new polymorphic form (form II) of the SD:4-ASA 1:1 cocrystal was discovered which could also be obtained by solvent evaporation from ethanol and acetone. Structure determination of the form II cocrystal was calculated using high resolution X-ray powder diffraction. The solubility of the SD:4-ASA 1:1 cocrystal was dependent on the pH and predicted by a model established for a two amphoteric component cocrystal. The form I cocrystal was found to be thermodynamically more stable in aqueous solution than form II, which showed transformation to form I. Dissolution studies revealed that the dissolution rate of SD from both cocrystals was enhanced when compared to a physical equimolar mixture and pure SD.Science Foundation Ireland (SFI) under Grant Number 07/SRC/B1158 and SFI/12/RC/2275

Improvement of physicochemical parameters of acyclovir using cocrystallization approach

ABSTRACT Acyclovir is an antiviral drug having potent activity against the virus of herpes family and varicella zoster. Unfortunately, drug suffers very poor oral bioavailability (15-30%). The main objective of present study was to develop acyclovir cocrystals with improved solubility which may result in improvement of bioavailability. Hansen solubility approach was used as a tool to predict the cocrystal formation of a drug with selected coformer. Cocrystals of acyclovir with various coformers were screened in order to enhance their water solubility. Cocrystals of the drug were prepared using various methods like solvent evaporation, wet grinding, and antisolvent addition. Formation of cocrystals by solvent evaporation method was found to be better method amongst all. Optimization of cocrystal formation was carried out by employing different solvents as well as the stoichiometric ratio of acyclovir with that of coformer. Synthesis of cocrystals was optimized using water as a solvent system resulted in good agreements. The potential cocrystal formation of acyclovir was characterized by IR, PXRD and DSC techniques. An in-vitro dissolution study was performed to determine the dissolution rate of cocrystals. The results suggest that acyclovir forms cocrystals with tartaric acid and the initial dissolution rate of synthesized cocrystals were considerably faster as compared to pure acyclovir

Pharmaceutical cocrystals : formation mechanisms, solubility behaviour and solid-state properties

The primary aim of pharmaceutical materials engineering is the successful formulation and process development of pharmaceutical products. The diversity of solid forms available offers attractive opportunities for tailoring material properties. In this context, pharmaceutical cocrystals, multicomponent crystalline materials with definite stoichiometries often stabilised by hydrogen bonding, have recently emerged as interesting alternative solid forms with potential for improving the physical and biopharmaceutical properties of a drug substance. There are, however, gaps in our understanding of the screening, scale-up and formulation operations required for effective use of cocrystals in drug product development. The objective of this thesis was to improve fundamental understanding of the formation mechanisms, solution behaviour and solid-state properties of pharmaceutical cocrystals. The solution chemistry and solubility behaviour of a diverse set of cocrystals were studied. It was found that the thermodynamic stability regions of the cocrystals and their components were defined by the phase solubility diagrams. Spray drying was introduced as a new method of preparing cocrystals; the formation mechanisms are illustrated. The cocrystals were more soluble than the respective drugs alone and the solubility-pH profiles were able to be predicted by mathematical models using a eutectic point determination approach. The cocrystal solubility was pH-dependent and could be engineered by the choice of coformers; this is valuable information for designing robust formulations. The solubility advantage of cocrystals was retained by the use of excipients that imparted kinetic and thermodynamic stability. The retention of drug-coformer association in processed cocrystals has been revealed, introducing a novel concept with potential implications for solid dosage form development. The final study demonstrated that the structure of the crystals and the particle engineering processes affected the solidstate and bulk particle properties of the cocrystals.This thesis contributes to the field of pharmaceutical science by advancing our understanding of crystallization processes and formulation development, thus enabling pharmaceutical cocrystals into drug products.Godkänd; 2012; 20120322 (amjalh); DISPUTATION Opponent: Professor emeritus Peter York, School of Pharmacy, University of Bradford, United Kingdom Ordförande: Professor Yelverton Tegner, Institutionen för Hälsovetenskap, Luleå tekniska universitet Tid: Torsdag den 26 april 2012, kl. 10.00 Plats: C305, Luleå tekniska universite

Pharmaceutical cocrystals : formation mechanisms, solubility behaviour and solid-state properties

The primary aim of pharmaceutical materials engineering is the successful formulation and process development of pharmaceutical products. The diversity of solid forms available offers attractive opportunities for tailoring material properties. In this context, pharmaceutical cocrystals, multicomponent crystalline materials with definite stoichiometries often stabilised by hydrogen bonding, have recently emerged as interesting alternative solid forms with potential for improving the physical and biopharmaceutical properties of a drug substance. There are, however, gaps in our understanding of the screening, scale-up and formulation operations required for effective use of cocrystals in drug product development. The objective of this thesis was to improve fundamental understanding of the formation mechanisms, solution behaviour and solid-state properties of pharmaceutical cocrystals. The solution chemistry and solubility behaviour of a diverse set of cocrystals were studied. It was found that the thermodynamic stability regions of the cocrystals and their components were defined by the phase solubility diagrams. Spray drying was introduced as a new method of preparing cocrystals; the formation mechanisms are illustrated. The cocrystals were more soluble than the respective drugs alone and the solubility-pH profiles were able to be predicted by mathematical models using a eutectic point determination approach. The cocrystal solubility was pH-dependent and could be engineered by the choice of coformers; this is valuable information for designing robust formulations. The solubility advantage of cocrystals was retained by the use of excipients that imparted kinetic and thermodynamic stability. The retention of drug-coformer association in processed cocrystals has been revealed, introducing a novel concept with potential implications for solid dosage form development. The final study demonstrated that the structure of the crystals and the particle engineering processes affected the solidstate and bulk particle properties of the cocrystals.This thesis contributes to the field of pharmaceutical science by advancing our understanding of crystallization processes and formulation development, thus enabling pharmaceutical cocrystals into drug products.Godkänd; 2012; 20120322 (amjalh); DISPUTATION Opponent: Professor emeritus Peter York, School of Pharmacy, University of Bradford, United Kingdom Ordförande: Professor Yelverton Tegner, Institutionen för Hälsovetenskap, Luleå tekniska universitet Tid: Torsdag den 26 april 2012, kl. 10.00 Plats: C305, Luleå tekniska universitet</p

Barnperspektiv vid ekonomiskt bistånd : Socialsekreterarnas syn på barns delaktighet t i handläggningsprocessen

Syftet med denna studie var att undersöka socialsekreterares uppfattning om barnperspektivet och dess tillämpningar i handläggningen av ekonomiskt bistånd. Sex socialsekreterare vid en enhet för ekonomiskt bistånd i Sverige intervjuades. Vi använde oss av teorin om gräsrotsbyråkrati och barndomssociologi som teoretiska perspektiv för att analysera resultaten. En tematisk analys genomfördes för det insamlade materialet, vilket ledde till tre huvudrubriker för resultatavsnittet: ”Innebörden av barnperspektiv”, ”Barnperspektiv i handläggningsprocessen” och ”Barns och ungas delaktighet i handläggningsprocessen”. Dessa rubriker fungerar som strukturerade delar som ligger i linje med våra frågeställningar. Resultatet visar att barnperspektivet är ett mångfacetterat begrepp utan en exakt definition. Socialsekreterare var kunniga om barnets perspektiv, men deras tolkningar och tillämpningar av det varierade. Studiendrar slutsatsen att socialarbetares tillämpning av barnperspektiv är beroende av flera faktorer, till exempel erfarenhet och auktoritetniv