Dynamic Vapor Sorption Analysis Research Articles

Characterization of the transition between the monohydrate and the anhydrous citric acid

The knowledge of the thermodynamic parameters related to the hydration of organic solid phases is paramount to exert a very good control over this transition during industrial production or storage. To study this phenomenon, the citric acid was chosen as a model compound. By an original combination of gravimetric and thermal analyses (dynamic vapor sorption and discontinuous isoperibolic thermal analysis, respectively) with structural determination (prototype of in situ X-ray diffractometer) the hydrate/anhydrate transition of the citric acid was thermodynamically characterized by determining: (i) the temperature associated to the peritectic transition ↔ + H2Ol, as well as (ii) the minimum relative humidity of hydration, and (iii) the critical relative humidity of deliquescence versus temperature. All these studies lead to the proposition of phase diagram between citric acid and water as a function of temperature and partial vapor pressure of water.

Cu(II) and Ni(II) complexes with a tri-, tetra- or hexadentate triethanolamine ligand: Structural characterization and properties

One Cu(II) (1) and two Ni(II) (2,3) novel compounds based on triethanolamine have been obtained and characterized by elemental and spectral analyses. Single-crystal X-ray crystallography has revealed that the crystal structure of compound 1 results from co-crystallization of ionic dinuclear [Cu2(H3L)2Cl2]Cl2 (1a) and molecular tetranuclear [Cu4(HL)2Cl4] (1b) species in a 1:0.036 ratio, both possessing an atrane structure. The molecular structure of [Ni2(H3L)2Cl2]Cl2 (3) resembles the compound [Cu2(H3L)2Cl2]Cl2 (1a). In both centrosymmetric dinuclear complexes, each metal atom exhibits an octahedral Cl2NO3 coordination provided by a tetradentate non-deprotonated triethanolamine ligand and two bridging chloride anions. The compound [Ni(H3L)2]Cl2 (2) has an ionic crystal structure, where triethanolamine acts as a non-deprotonated tridentate ligand, one of the OH-groups not being involved in coordination to the Ni atom. Analysis of the magnetic susceptibility results for compounds 1–3 reveals the presence of an antiferromagnetic interaction in the case of the Cu-based dimer 1 (J=−1.99(7)cm−1, g=2.07(9)) and a ferromagnetic interaction for the Ni-based dimer 3 (J=+7.17(3)cm−1, g=2.35(2)) with the ground state S=2. A significant zero field splitting (ZFS) effect was found for the Ni(II)-based complexes (D=−6.5cm−1, E=0.4cm−1). The thermal stability of the compounds was studied under a nitrogen atmosphere. The biocidal activities against some fungi (Aspergillus niger ATCC 53346, Penicillium frequentans ATCC 10110, Alternaria alternate ATCC 8741) and bacteria (Pseudomonas aeroginosa ATCC 27813 and Bacillus sp. ATCC 15970) were also evaluated. The moisture behavior of the obtained crystalline compounds was studied by dynamic water vapor sorption analysis.

Metallopolymeric structures containing highly flexible siloxane sequence

H-bonded supramolecular polymers based on 1,3-bis(3-carboxypropyl)tetramethyldisiloxane and 4,4′-azopyridine, 1, or imidazole, 3, were prepared and used as ligands for Co(II) and Zn(II) ions, respectively. A re-organization of the supramolecular structures occurred by introducing the metal salts, Co(ClO4)2 × 6H2O and Zn(O2CCH3)2 × 2H2O, leading to the polyorganometallosiloxane structures 2 and 4, respectively. The compounds were investigated by elemental and spectral (1H NMR, FTIR, UV–Vis, and fluorescence) analysis as well as by X-ray single crystal diffraction. Thermal behaviour of the metallopolymers was evaluated by TGA and DSC while the moisture behaviour was studied by dynamic vapour sorption analysis (DVS). Magnetic susceptibility was determined for paramagnetic Co(II)-containing polyorganometallosiloxane. The dielectric response and ac conductivity were investigated by dielectric spectroscopy at different temperatures and frequencies.

Dynamic Moisture Sorption Characteristics of Xerogels from Water-Swellable Oligo(oxyethylene) Lignin Derivatives

Highly swellable lignin derivatives were prepared by cross-linking of oxidatively preactivated spruce organosolv lignin (OSL) with poly(ethylene) glycol diglycidyl ether (PEGDGE). The lignin gels obtained are considered to be an environmentally friendly alternative to synthetic hydrogels and superabsorbents and represent a novel type of lignin based functional materials. For their application, it is not only the absorption of water in terms of hydrogel swelling that plays an important role, but also the adsorption and retention of moisture by the corresponding xerogels. To reveal the mechanisms involved in moistening and reswelling of the lignin gels, the interaction of water vapor with lyophilized xerogels was investigated and compared with sorption characteristics of parent lignin. The chemical structure of PEGDGE-modified lignin was investigated using attenuated total reflectance Fourier-transformed infrared spectroscopy and selective aminolysis and was related to its sorption and swelling characteristics. Bound and free water in hydrogels was determined by differential scanning calorimetry and by measuring the free swelling capacity of the gels. Moisture sorption of OSL and PEGDGE-modified lignin xerogels was determined using dynamic vapor sorption analysis. In order to determine monolayer and multilayer sorption parameters, sorption data were fitted to the Brunauer-Emmett-Teller and the Guggenheim-Anderson-de Boer model. Swelling properties of the hydrogels and moisture sorption of the corresponding xerogels were found to be strongly dependent on the degree of chemical modification with PEGDGE: Total and free water content of hydrogels decrease with increasing cross-linking density; on the other hand, water bound in hydrogels and moisture sorption of xerogels at high levels of water activity strongly increase, presumably because of the hydration of hydrophilic oligo(oxyethylene) and oligo(oxyethylene) glycol substituents, which lead to moisture diffusion into the xerogel matrix, plasticization, and swelling of the gels.

Exploring the Solid-Form Landscape of Pharmaceutical Hydrates: Transformation Pathways of the Sodium Naproxen Anhydrate-Hydrate System

To understand the transformation pathways amongst anhydrate/hydrate solid forms of sodium naproxen and to highlight the importance of a polymorphic dihydrate within this context. Multi-temperature dynamic vapour sorption (DVS) analysis combined with variable-humidity X-ray powder diffraction (XRPD) to establish the transformation pathways as a function of temperature and humidity. XRPD and thermogravimetric analysis (TGA) to characterise bulk samples. Monitoring of in-situ dehydration using solid-state (13)C CP/MAS spectroscopy. At 25 °C, anhydrous sodium naproxen (AH) transforms directly to one dihydrate polymorph (DH-II). At 50 °C, AH transforms stepwise to a monohydrate (MH) then to the other dihydrate polymorph (DH-I). DH-II transforms to a tetrahydrate (TH) more readily than DH-I transforms to TH. Both dihydrate polymorphs transform to the same MH. The properties of the polymorphic dihydrate control the transformation pathways of sodium naproxen.

Hydrogen-bonded supramolecular polymers containing dimethylsilane groups: Synthesis, crystal structure, and characterization

Bis[N-(4-carboxyphenyl)phtalimidyl]dimethylsilane prepared by the reaction between bis(3,4-dicarboxyphenyl)dimethylsilane anhydride and p-aminobenzoic acid has been used to built three novel hydrogen-bonded supramolecular polymers as a result of cocrystallization with pyridine derivatives: 4,4′-bipyridyl (SP1), 1,2-bis(4-pyridyl)ethylene (SP2), and 4,4′-azopyridine (SP3). The structures of the dianhydride, diacid, and derived supramolecular polymers were investigated by Fourier transform infrared (FTIR) and proton magnetic resonance (1H NMR) spectroscopy. Self-assembling was proved by the presence of the IR absorption bands around 1900 and 2400 cm−1 specific for hydrogen bond. The association constant values were estimated by using FTIR spectroscopy in solid state. According to X-ray diffraction study, the bis(3,4-dicarboxyphenyl)dimethylsilane anhydride (1) has an isolated molecular structure. Bis[N-(4-carboxyphenyl)phtalimidyl]dimethylsilane (2) molecules are associated in the crystal structure via dimeric OH…O hydrogen bonds resulting in the wavy 1D supramolecular chain. The main packing motif for SP1 and SP3 is represented by wavy chain formed by alternating sequences of 4,4′-bipyridyl or 4,4′-azopyridine and bis[N(4-carboxyphenyl)phtalimidyl]dimethylsilane molecules linked by OH…N hydrogen bonds. Thermal behavior was studied by differential scanning calorimetry and thermogravimetric analysis. The ability for the structuration in film was emphasized by atomic force microscopy. The molecular transport ability of the reversible associations was estimated by dynamic water vapor sorption (DVS) analysis. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

Comparison of physico-chemical characteristics among three pharmaceutical spherical carbon adsorbents

In this study, various physicochemical characteristics were evaluated for three pharmaceutical spherical carbon adsorbents, Kremezin as a brand product and its generics; Merckmezin and Spherical Carbon Adsorbent “Mylan”. Scanning electron microscopic observations, measurements of specific surface area, particle sizes, and pore volume distributions by mercury intrusion porosimetry, and dynamic vapor sorption (DVS) analysis were conducted. Compared to Kremezin, Merckmezin is dented with a small pore-rich structure; pores of less than 10nm make up 43% (Kremezin) and 68% (Merckmezin) of total pore volume. On the other hand, Spherical Carbon Adsorbent “Mylan” is porous with macropores. The results of fractal dimension analysis of micropores suggested that the complexity of the internal pore structure is Merckmezin>Kremezin≫Spherical Carbon Adsorbent “Mylan”. The three spherical carbon adsorbents are physico-chemically different, but clinical studies should be conducted to prove that they are therapeutically equivalent.

Zinc oxide-linen fibrous composites: morphological, structural, chemical and humidity adsorptive attributes

The main result and characterizing aspect of the research consists of the effectiveness of novel ZnO-linen fibrous composites synthesized by means of hydrothermal deposition of zinc oxide onto linen fibers, with the assistance of two surfactants. This has a direct implication on the relationship between the morphological, structural and chemical attributes and water vapor sorption-desorption behavior. Methodology consists of the hydrothermal synthesis of zinc oxide onto linen fibrous substrates previously grafted with MCT-β-CD (MonoChloroTriazinyl–β-CycloDextrin) via a hydrothermal process. The morphological, structural and chemical properties of the samples were examined, in terms of a co-assisted investigation system: SEM images for the morphology, EDX analysis for surface composition, FTIR spectroscopy and X-ray diffractometry for structural samples features. Dynamic vapor sorption (DVS) analysis will complete this study. According to the results provided by the characterization technique, the uniformity of the fabric coated with ZnO powder hydrothermally synthesized with assistance of CTAB (Cetyl TrimethylAmmonium Bromide) is better than that of ZnO powder hydrothermally synthesized in the presence of Pluronic P123 and possesses good washing fastness. X-ray diffraction results have indicated that the composites exhibited a more ordered structure and higher water vapor sorption-desorption capacity (obtained by DVS analysis) compared with those of the reference fibrous linen supports.

Polymorphs and a Hydrate of Furosemide–Nicotinamide 1:1 Cocrystal

Five anhydrous polymorphs (forms I–V) and one hydrate of furosemide–nicotinamide 1:1 cocrystal were discovered, and their solid-state properties were characterized using X-ray powder diffraction and differential scanning calorimetry. The crystal structures of forms I–IV were determined from the X-ray powder diffraction data and showed the structural differences between forms, which are mainly attributable to molecular conformations and supramolecular synthons. The slurry conversion experiments revealed that the order of thermodynamic stability of the polymorphs at 25 °C is I > III > II > V > IV. Dynamic vapor sorption analysis and X-ray single-crystal structure determination of the hydrate were conducted to study the dehydration mechanism. We observed structural similarities between the hydrate and its dehydrate, form IV, such as lattice parameters (except the a-axis length), synthons between furosemide and nicotinamide molecules, and the molecular conformation of furosemide; after dehydration, however, the a-axis contracted and nicotinamide molecules were displaced, along with the pyridine ring twisting.

Solid‐state characterization of novel active pharmaceutical ingredients: Cocrystal of a salbutamol hemiadipate salt with adipic acid (2:1:1) and salbutamol hemisuccinate salt

The production of salt or cocrystalline forms is a common approach to alter the physicochemical properties of pharmaceutical compounds. The goal of this work was to evaluate the impact of anion choice (succinate, adipate, and sulfate) on the physicochemical characteristics of salbutamol forms. Novel crystals of salbutamol were produced by solvent evaporation: a cocrystal of salbutamol hemiadipate with adipic acid (salbutamol adipate, SA), salbutamol hemisuccinate tetramethanolate (SSU.MeOH), and its desolvated form (SSU). The crystalline materials obtained were characterized using thermal, X-ray, nuclear magnetic resonance, Fourier transform infrared spectroscopy, dynamic vapor sorption (DVS), and elemental analysis. The crystal forms of SA and SSU.MeOH were determined to be triclinic, (Pī), and monoclinic, (P2(1) /n), respectively. DVS analysis confirmed that SSU and SA do not undergo hydration under increased relative humidity. Both thermal and elemental analyses confirmed the stoichiometry of the salt forms. The aqueous solubilities of SA and SSU were measured to be 82 ± 2 mg/mL (pH 4.5 ± 0.1) and 334 ± 13 mg/mL (pH 6.6 ± 0.1), respectively. Measured values corresponded well with the calculated pH solubility profiles. The intrinsic dissolution rate of cocrystallized SA was approximately four times lower than that of SSU, suggesting its use as an alternative to more rapidly dissolving salbutamol sulfate.

Thermo-physical characterization of Pharmacoat® 603, Pharmacoat® 615 and Mowiol® 4-98

Hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA) are important polymers in pharmaceutical, food and other industries being largely used as encapsulation agents. The characterization of two reference grades of HPMC (Pharmacoat® 603 and Pharmacoat® 615) and one reference grade of PVA (Mowiol® 4-98), through X-ray diffraction (XRD) and thermogravimetry (TG) is described. Specific analyses were performed by means of dynamic vapour sorption analysis of water adsorption/desorption from vapours at 10, 25, 40, 55 and 70 °C. Guggenheim–Anderson–de Boer (GAB), Brunauer–Emmett–Teller (BET), Park and n-layer BET models were successfully used to fit the experimental data. The glass transition temperature as function of water content was measured by means of differential scanning calorimetry (DSC). The experimental data were analysed according to Linear, Gordon–Taylor, Fox and Roos equations. XRD studies revealed amorphous structure for the Pharmacoat® 603 and Pharmacoat® 615 and crystalline for Mowiol® 4-98. Single and multi-step temperature degradation point was found for Pharmacoat® 603 and Pharmacoat® 615 and Mowiol® 4-98, respectively. The water uptake is higher for Pharmacoat® 603 and Pharmacoat® 615 than Mowiol® 4-98. The influence of temperature on water uptake is opposite for the two types of polymers. GAB and n-layer BET were found to better model Pharmacoat® 603 and Pharmacoat® 615 and Mowiol® 4-98 data, respectively. The water makes the glass transition to decrease quite drastically. Gordon–Taylor is better fitting the experimental data both for Pharmacoat® 603 and Pharmacoat® 615 and Mowiol® 4-98.

Dynamic Moisture Sorption Characteristics of Enzyme-Resistant Recrystallized Cassava Starch

The interaction of moisture with enzyme-resistant recrystallized starch, prepared by heat-moisture treatment of debranched acid-modified or debranched non-acid-modified cassava starch, was investigated in comparison with the native granules. Crystallinities of the powdered products were estimated by X-ray diffraction. Moisture sorption was determined using dynamic vapor sorption analyzer and data fitted to various models. Percent crystallinities of native starch (NS), non-acid-modified recrystallized starch (NAMRS), and acid-modified recrystallized starch (AMRS) were 39.7, 51.9, and 56.1%, respectively. In a(w) below 0.8, sorption decreased in the order NS > NAMRS > AMRS in line with increasing sample crystallinities but did not follow this crystallinity dependence at higher a(w) because of condensation and polymer dissolution effects. Adsorbed moisture became internally absorbed in NS but not in NAMRS and AMRS, which might explain the high resistance of the recrystallized starches to digestion because enzyme and starch cannot approach each other over fairly sufficient surface at the molecular level.

Preparation and characterisation of novel chlorothiazide potassium solid-state salt forms: Intermolecular self assembly suprastructures

Chlorothiazide (CTZ) is a poorly soluble diuretic agent. The aim of the present work was to produce and characterise a potassium salt form of chlorothiazide which has the potential advantages of improved aqueous solubility and potassium supplementation. A number of novel potassium salt forms of CTZ (CTZK) were prepared: CTZK monohydrate (form I), CTZK dihydrate (form II), anhydrous CTZK (form III), CTZK monohydrate hemiethanolate (form IV) and a desolvate of CTZK monohydrate hemiethanolate (form V). These salt forms were characterised by thermal analysis, PXRD, NMR, elemental analysis, FTIR, Karl Fisher titrimetry, ICP-MS and GC–MS. The ethanol-free CTZK forms were also characterised by dynamic vapour sorption analysis (DVS). CTZK form I was stable (in the DVS) over the range 0–60% RH. The dihydrate form of the salt was stable (in the DVS) over a broader range of relative humidities, 10–90% RH at 25°C. CTZK form II was less hygroscopic at high humidities (70–90% RH) than the previously reported CTZNa dihydrate. Single crystal X-ray analysis indicated that chlorothiazide potassium, crystallised from water or water/acetone mixture, formed a dihydrated polymeric-like intermolecular self-assembly (ISA) suprastructure. The ISA coordination was determined to be: (CTZ)3·K·(H2O)2(CTZ)2·(H2O)2·K·(CTZ)3 (monoclinic, space group: C2/c, single crystal cell parameters: a=18.328(4)Å, b=7.3662(16)Å, c=19.993(5)Å, α=90°, β=99.729(3)°, γ=90°). When CTZK was crystallised from ethanol, a monohydrate hemiethanolate ISA was formed, described as (CTZ)3·K·CTZ·(H2O)2·CTZ·K·(CTZ)2 (triclinic, space group: P-1, single crystal cell parameters: a=7.078(3)Å, b=9.842(5)Å, c=21.994(11)Å, α=87.522(13)°, β=84.064(14)°, γ=78.822(12)°). The aqueous solubility of CTZK dihydrate, was determined to be 78.71±1.82mg/ml, approximately 400-fold higher than chlorothiazide, indicating a biopharmaceutical advantage associated with the potassium salt form.

Development and characterisation of soluble polymeric particles for pulmonary peptide delivery

Pulmonary administration of protein and peptide drugs using inhaled dry powder particles is an interesting alternative to parenteral delivery. The stabilisation of these molecules is essential to the maintenance of biological activity in such inhalation formulations. Here salmon calcitonin (sCT) was co-spray dried with linear or branched PEG (L-PEG and B-PEG) and PVP in order to formulate aerosolisable particles of the bioactive peptide. Co-spray drying L-PEG and PVP resulted in porous particles, with minimal D 50 (median volume diameter) and MMAD (mass median aerodynamic diameter) values obtained for a PEG/PVP w/w ratio of 1. For particles based on both L-PEG and B-PEG, an increase in acetone, a poor solvent for the PVP, up to 70 wt% of the spray dried solution led to a decrease in D 50 and MMAD. Crystallinity of PEG in the particles ranged between 90 and 97% when the PVP content varied between 15 and 70 wt%, indicating a low degree of interaction between PVP and PEG. Additionally, dynamic vapour sorption analysis showed that an increase in PVP content increased the particle surface hygroscopicity. Hence, particle properties were adjusted by altering the water/acetone and PEG/PVP ratio in the spray dried solutions. PVP present at the particles surface protects them from melting during the spray drying process but also increases their hygroscopicity, adversely affecting their aerodynamic properties. Targeting a 5 wt% of sCT loading resulted in a loading efficiency of 77.9 and 83.6% with L-PEG and B-PEG-based particles, respectively. Loading of sCT in L-PEG or B-PEG-based particles modified particle roughness and D 50 , leading to an increase in MMAD of the L-PEG-based particles. However, particles were still considered to be suitable for aerosolisation as their FPFs (fine particle fractions) were higher than 30%. These particles formulated with PVP and PEG allowed sCT biological activity to be maintained when evaluated by measuring cAMP production by T47D cells.

Interaction of Water with Three Granular Biopesticide Formulations

Two obstacles for biopesticide commercialization, long shelf life and reliable efficacy, are both affected by moisture availability. Three biopesticide delivery systems, TRE-G, PEC-G, and PESTA, were analyzed by dynamic vapor sorption analysis. The objective was to investigate the moisture sorption profile of each system in air at 25 degrees C and a relative humidity (RH) ranging from 0 to 90%. The formulations sorbed up to 12.7% moisture. In rehydrating from 0.00 to 90% RH, TRE-G and PEC-G were >or=63% and >or=58% faster than Pesta, respectively. In losing moisture from 90 to 0.00% RH, Pesta was 3.4 and 2.3 times slower than TRE-G and PEC-G, respectively. The GAB model was inadequate for describing moisture sorption, but the Young and Nelson model showed good correlation (r > 0.990) for all three formulations. Moisture distribution for all formulations was obtained. The implications of the findings as they relate to shelf life and dew period requirements of biopesticides are discussed.

Characterization of Moisture‐Protective Polymer Coatings Using Differential Scanning Calorimetry and Dynamic Vapor Sorption

The aim of this study was to evaluate the moisture‐protective ability of different polymeric coatings. Free films and film‐coated tablets (with cores containing freeze‐dried garlic powder) were prepared using aqueous solutions/dispersions of hydroxypropyl methylcellulose (HPMC), Opadry® AMB [a poly(vinylalcohol)‐based formulation] and Eudragit® E PO [a poly(methacrylate–methylmethacrylate)]. The water content of the systems upon open storage at 75% relative humidity (RH) and 22°C (room temperature) was followed gravimetrically. Furthermore, polymer powders, free films and coated tablets were analyzed by differential scanning calorimetry (DSC) and dynamic vapor sorption (DVS). The type of polymer strongly affected the resulting water uptake kinetics of the free films and coated tablets. DSC analysis revealed whether or not significant physical changes occurred in the coatings during storage, and whether the water vapor permeability was water concentration dependent. Using DVS analysis the critical glass transition RH of Opadry® AMB powder and Opadry® AMB‐coated tablets at 25°C could be determined: 44.0% and 72.9% RH. Storage below these threshold values significantly reduces water penetration. Thus, DVS and DSC measurements can provide valuable information on the nature of polymers used for moisture protection. © 2008 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:651–664, 2009

Investigations on the Humidity-Induced Transformations of Salbutamol Sulphate Particles Coated with l-Leucine

The crystallization and structural integrity of micron-sized inhalable salbutamol sulphate particles coated with L-leucine by different methods are investigated at different humidities. The influence of the L-leucine coating on the crystallization of salbutamol sulphate beneath the coating layer is explored. The coated particles are prepared by an aerosol flow reactor method, the formation of the L-leucine coating being controlled by the saturation conditions of the L-leucine. The coating is formed by solute diffusion within a droplet and/or by vapour deposition of L-leucine. The powders are humidified at 0%, 44%, 65% and 75% of relative humidity and the changes in physical properties of the powders are investigated with dynamic vapour sorption analysis (DVS), a differential scanning calorimeter (DSC), and a scanning electron microscope (SEM). Visual observation show that all the coated particles preserve their structural integrity whereas uncoated salbutamol sulphate particles are unstable at 65% of relative humidity. The coating layer formed by diffusion performs best in terms of its physical stability against moisture and moisture-induced crystallization. The degree of crystallization of salbutamol in the as-prepared powders is within the range 24-35%. The maximum degree of crystallization after drying ranges from 55 to 73% when the salbutamol crystallizes with the aid of moisture. In addition to providing protection against moisture, the L-leucine coating also stabilizes the particle structure against heat at temperatures up to 250 degrees C. In order to preserve good flowability together with good physical stability, the best coating would contain two L-leucine layers, the inner layer being formed by diffusion (physical stability) and the outer layer by vapour deposition (flowability).

Crystallization and Crystallinity of Fluticasone Propionate

Solubilization of fluticasone propionate (FP) was effected using aqueous solutions of (i) different grades of poly(ethylene glycol) (PEG), (ii) methanol, and (iii) acetone to enable antisolvent crystallization by the addition of water. The solubility of FP in acetone was significantly higher than in PEG 400 or PEG 6000, and FP solubility was observed to be nonideal in either cosolvent. Crystallization of FP was instantaneous upon addition of water as antisolvent, with nucleation occurring during the mixing phase. The smallest crystals were produced in all cases from PEG solvents, which was attributed to a greater degree of nucleation and microcrystals of a size-range were produced. Crystals produced from PEG solvents also displayed a resistance to agglomeration and Ostwald ripening, which was observed to affect the morphology of FP crystallized from either methanol or acetone by the addition of water. In spite of the very rapid kinetics of solid formation, FP crystallized as the stable Form I polymorph from PEG 400 and PEG 6000. Conversely, mechanical milling of highly crystalline particles resulted in the generation of disorder in the crystals, which was apparent from surface dynamic vapor sorption analysis. The generation of FP microcrystals with a small size range from environmentally benign PEG solvents as the stable crystalline form represents an improvement over current crystallization and micronization techniques for the production of inhalable FP.

Role of Water in the Physical Stability of Solid Dosage Formulations

The interaction of moisture with pharmaceutical solids is highly crucial to an understanding of water-based processes, for example, manufacturing processes or prediction of solid dosage form stability and shelf life. Both the active pharmaceutical ingredient (API) and excipients in the formulation have different moisture sorption properties that can result in unexpected processing-induced phase transitions and they can affect solid-state phase transitions in the final dosage forms. The character of excipient effects on the stability of formulation. Phase transformations in formulations can lead to instability in physicochemical, biopharmaceutical, and processing properties of products. The aim of the present study was to investigate the water sorption properties of different excipients, model the sorption isotherms, examine the phase transitions, and identify differences of excipients in solid dosage form stability using dynamic vapor sorption analysis, near-infrared spectroscopy, and X-ray diffraction methods. The thermal processing was carried out with a variable temperature X-ray powder diffractometer to compare the dehydration behavior of wet excipients and evaluate solid-state properties during heating. These results showed that despite some limitations, moisture sorption isotherms of excipients are useful in predicting solid-state stability, interactions at early stages of formulation development, and effects of moisture on physicochemical properties of the final dosage forms.

Water Distribution Studies Within Microcrystalline Cellulose and Chitosan using Differential Scanning Calorimetry and Dynamic Vapor Sorption Analysis

The objective of the study was to assess and compare the interaction and distribution of water within microcrystalline cellulose (MCC) and chitosan by differential scanning calorimetry (DSC) and dynamic vapor sorption analysis. The amounts of nonfreezing and freezing water in hydrated samples were determined from melting endotherms obtained by DSC. After accounting for the percent crystallinity of MCC and chitosan, no statistically significant difference was observed in their ability to bind water molecules per repeating unit at the minimum water content at which freezing water is evident. Exposure of chitosan to water for 30 min was sufficient to achieve equilibration at 61% w/w actual water content. The moisture sorption profiles were analyzed according to the GAB and Young and Nelson equations. The adsorbed monolayer, externally adsorbed moisture, and internally absorbed moisture were not statistically different for MCC and chitosan after accounting for the amorphous content of the polymers. These studies suggest that chitosan can act as a “molecular sponge,” and thus aid in the production of beads by extrusion and spheronization. © 2004 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 93: 1766–1779, 2004