International Journal of Pharmaceutics (v.462, #1-2)
EDITORIAL BOARD (iii).
A novel aqueous parenteral formulation of docetaxel using prodrugs by Min-Ho Park; Chang-Gu Keum; Jae-Young Song; Daehee Kim; Cheong-Weon Cho (1-7).
Effects of the formulations (A) on cell viability in HepG2 cells; (B) on hemolytic activity. Control means Taxotere® formulation.The aim of this study is to develop an aqueous parenteral solution of docetaxel using prodrugs. Docetaxel (DTX) is a highly lipophilic drug and practically insoluble in water. To overcome insolubility of docetaxel, three kinds of docetaxel prodrugs were synthesized using succinyl linker such as DTX-G, DTX-L or DTX-S and physicochemically characterized. The solubility of docetaxel prodrugs was determined by changing the concentration and type of surfactants, cosolvents or cyclodextrins. It was observed that the novel mixture of 15% PEG 400, 2.5% Tween 80 and 20% hydroxypropyl-β-cyclodextrin significantly increased the solubility of DTX-G up to 5.7 mg/mL. After subjected to the study of the hemolytic and cytotoxic activities, it was shown that the novel mixture did not show the hemolysis compared to Taxotere®. It was suggested this novel mixture might have the potential to develop an aqueous parenteral formulation.
Keywords: Docetaxel; Prodrug; Parenteral; Solubility; Hemolysis;
Distribution of binder in granules produced by means of twin screw granulation by Margot Fonteyne; Andrew Luke Fussell; Jurgen Vercruysse; Chris Vervaet; Jean Paul Remon; Clare Strachan; Thomas Rades; Thomas De Beer (8-10).
According to the quality by design principle processes may not remain black-boxes and full process understanding is required. The granule size distribution of granules produced via twin screw granulation is often found to be bimodal. The aim of this study was to gain a better understanding of binder distribution within granules produced via twin screw granulation in order to investigate if an inhomogeneous spread of binder is causing this bimodal size distribution. Theophylline–lactose–polyvinylpyrrolidone K30 (PVP) (30–67.5–2.5%, w/w) was used as a model formulation. The intra-granular distribution of PVP was evaluated by means of hyperspectral coherent anti-Stokes Raman scattering (CARS) microscopy. For the evaluated formulation, no PVP rich zones were detected when applying a lateral spatial resolution of 0.5 μm, indicating that PVP is homogenously distributed within the granules.
Keywords: Twin screw granulation; Binder distribution; CARS;
Development of Salvianolic acid B–Tanshinone II A–Glycyrrhetinic acid compound liposomes: Formulation optimization and its effects on proliferation of hepatic stellate cells by Jiahao Lin; Xiuli Wang; Qing Wu; Jundong Dai; Huida Guan; Weiyi Cao; Liangying He; Yurong Wang (11-18).
The aim of this study was to systematically optimize and characterize the co-encapsulation process of Salvianolic acid B (Sal B), Tanshinone II A (TSN) and Glycyrrhetinic acid (GA) into liposomes. The liposomes (GTS-lip) were prepared using film hydration method combined with probe sonication to encapsulate two hydrophobic components (TSN and GA), and using pH gradient method to load hydrophilic component Sal B. The concentration of encapsulated drugs was measured by a reversed phase high performance liquid chromatography (RP-HPLC) method. Systematic optimization of encapsulation process was performed using single factor test, orthogonal test in combination with Box–Behnken Design. Optimum conditions are as follows: ratio of GA to lipid (w/w) = 0.08, ratio of Sal B to lipid (w/w) = 0.12 and pH of buffer = 3.3. Based on the conditions mentioned above, encapsulation efficiency of Sal B, TSN and GA reached target levels: (96.03 ± 0.28)%, (80.63 ± 0.91)% and (88.56 ± 0.17)%, respectively. The GTS-lip had a unimodal size-distribution and a mean diameter of 191.3 ± 6.31 nm. Morphology determination of the GTS-lip indicated that the liposomes were spherical, and there was no free drug crystal in the visual field of transmission electron microscopy. Also, the ζ potential of GTS-lip was detected to be −11.6 ± 0.35 mV. In vitro release investigation of GTS-lip suggested that the release rate of GTS-lip significantly decreased compared to drug solution. The accumulative release percentage of TSN, GA and Sal B were 10% in 36 h, 4% in 36 h and 77% in 24 h. Meanwhile, GTS-lip exhibited definite activity on proliferative inhibition of hepatic stellate cells (HSC). GTS-lip decreased the viability of the HSC to higher than 75% at two high drug concentration groups in 24 h. At the same time, GTS-lip of two low drug concentration groups increased the inhibition rates by 2.3 folds and 1.9 folds separately at 48 h compared to 24 h. By contrast, inhibition activity of G-T-S solution group showed less change between 48 h and 24 h. The prolonged and enhanced activity in 48 h which GTS-lip group manifested might contribute to its sustained release effect.
Keywords: Co-delivery; Salvianolic acid B; Tanshinone II A; Glycyrrhetinic acid; Liposomes; Hepatic stellate cells;
NanoCluster budesonide formulations enable efficient drug delivery driven by mechanical ventilation by Warangkana Pornputtapitak; Nashwa El-Gendy; Joel Mermis; Amy O’Brien-Ladner; Cory Berkland (19-28).
Agglomerates of budesonide nanoparticles (also known as ‘NanoClusters’) are fine dry powder aerosols that were hypothesized to enable drug delivery through ventilator circuits. These engineered powders were delivered via a Monodose® inhaler or a novel device, entrained through commercial endotracheal tubes, and analyzed by cascade impaction. Inspiration flow rates and other parameters such as inspiration patterns and inspiration volumes were controlled by a ventilator. NanoCluster budesonide (NC-Bud) formulations had a higher efficiency of aerosol delivery compared to micronized budesonide with NC-Bud showing a much higher percent emitted fraction (%EF). Different inspiration patterns (sine, square, and ramp) did not affect the powder performance of NC-Bud when applied through a 5.0 mm endotracheal tube. The aerosolization of NC-Bud also did not change with the inspiration volume (1.5–2.5 L) nor with the inspiration flow rate (20–40 L/min) suggesting fast emptying times for budesonide capsules. The %EF of NC-Bud was higher at 51% relative humidity compared to 82% RH. The novel device and the Monodose® showed the same efficiency of drug delivery but the novel device fit directly to a ventilator and endotracheal tubing connections. The new device combined with NanoCluster formulation technology allowed convenient and efficient drug delivery through endotracheal tubes.
Keywords: Budesonide; NanoCluster; Mechanical ventilation; Dry powder inhalers; Inhalation;
Nanometer depth resolution in 3D topographic analysis of drug-loaded nanofibrous mats without sample preparation by Urve Paaver; Jyrki Heinämäki; Ivan Kassamakov; Edward Hæggström; Tuomo Ylitalo; Anton Nolvi; Jekaterina Kozlova; Ivo Laidmäe; Karin Kogermann; Peep Veski (29-37).
We showed that scanning white light interferometry (SWLI) can provide nanometer depth resolution in 3D topographic analysis of electrospun drug-loaded nanofibrous mats without sample preparation. The method permits rapidly investigating geometric properties (e.g. fiber diameter, orientation and morphology) and surface topography of drug-loaded nanofibers and nanomats. Electrospun nanofibers of a model drug, piroxicam (PRX), and hydroxypropyl methylcellulose (HPMC) were imaged. Scanning electron microscopy (SEM) served as a reference method. SWLI 3D images featuring 29 nm by 29 nm active pixel size were obtained of a 55 μm × 40 μm area. The thickness of the drug-loaded non-woven nanomats was uniform, ranging from 2.0 μm to 3.0 μm (SWLI), and independent of the ratio between HPMC and PRX. The average diameters (n = 100, SEM) for drug-loaded nanofibers were 387 ± 125 nm (HPMC and PRX 1:1), 407 ± 144 nm (HPMC and PRX 1:2), and 290 ± 100 nm (HPMC and PRX 1:4). We found advantages and limitations in both techniques. SWLI permits rapid non-contacting and non-destructive characterization of layer orientation, layer thickness, porosity, and surface morphology of electrospun drug-loaded nanofibers and nanomats. Such analysis is important because the surface topography affects the performance of nanomats in pharmaceutical and biomedical applications.
Keywords: Surface topography analysis; Nanofibers; Scanning white light interferometry (SWLI); Scanning electron microscopy (SEM); Electrospinning; Piroxicam;
The evaluation of the biomedical effectiveness of poly(amido)amine dendrimers generation 4.0 as a drug and as drug carriers: A systematic review and meta-analysis by Marian Jędrych; Katarzyna Borowska; Ryszard Galus; Barbara Jodłowska-Jędrych (38-43).
The purpose of this study was to investigate the evaluation of the biomedical effectiveness of poly(amido)amine dendrimers generation 4.0 (PAMAM G4) as a drug and as drug carriers by a systematic review of literature and meta-analysis. The results obtained from meta-analysis concluded that drug therapy reduces the change of parameters in relation to the control. The impact of the drug administered to change the test parameters are dependent on the type of tissue. PAMAM G4 may be effective in vitro and in vivo as a drug and drug carriers and may have appropriate applications in various fields of medicine. PAMAM G4 dendrimers hold promises for nanomedicine.
Keywords: Poly(amido)amine dendrimers; Generation 4.0; PAMAM G4; Review; Meta-analysis;
A new concept for the treatment of atopic dermatitis: Silver–nanolipid complex (sNLC) by C.M. Keck; P. Anantaworasakul; M. Patel; S. Okonogi; K.K. Singh; D. Roessner; R. Scherrers; K. Schwabe; C. Rimpler; R.H. Müller (44-51).
In the treatment of mild to medium severe atopic dermatitis a new formulation proved to be highly efficient. The formulation is based on a combination of microsilver and nanolipid carriers (NLC) incorporated into an o/w cream and a lotion. A theory of action was proposed, the formation of silver–NLC complex (sNLC). In this study this theory was proven, and based on this new mechanism two new approaches for dealing with AD are suggested to distinctly improve AD treatment, i.e. increasing efficiency, reducing drug exposure and reducing side effects. The antimicrobial silver ions adsorb onto the surface of the negatively charged NLC (=sNLC complex). The sNLC as nanoparticles are highly adhesive to skin and bacterial surfaces, leading to a locally high concentration of silver ions killing the bacteria, much more effective than silver alone. The NLC restore the distorted skin barrier. Based on this a new two-step approach is suggested: (1) “treatment-supportive consumer care” by restoring the normal skin condition (NLC for barrier restoration plus synergistic antibacterial silver–NLC complex) and (2) “drug-loaded consumer care AD formulations”. i.e. incorporating drugs into the NLC of this consumer care formulation. NLC incorporation makes the drugs more effective (penetration enhancement) and simultaneously exploits the skin normalization ability of the skin care sNLC formulation, future drug candidates being prednicarbate and tacrolimus.
Keywords: Nanostructured lipid carriers (NLC); Silver; Atopic dermatitis; Silver–NLC-complex; Skin; Nanosensitive;
An interfacially plasticized electro-responsive hydrogel for transdermal electro-activated and modulated (TEAM) drug delivery by Sunaina Indermun; Yahya E. Choonara; Pradeep Kumar; Lisa C. du Toit; Girish Modi; Regina Luttge; Viness Pillay (52-65).
This paper highlights the use of hydrogels in controlled drug delivery, and their application in stimuli responsive, especially electro-responsive, drug release. electro-conductive hydrogels (ECHs) displaying electro-responsive drug release were synthesized from semi-interpenetrating networks (semi-IPNs) containing a poly(ethyleneimine) (PEI) and 1-vinylimidazole (VI) polymer blend as the novel electro-active species. The semi-IPNs are systems comprised of polyacrylic acid (PAA) and poly(vinyl alcohol) (PVA). This paper attempts to investigate the various attributes of the electro-responsive ECHs, through institution of a statistical experimental design. The construction of a Box–Behnken design model was employed for the systematic optimization of the ECH composition. The design model comprised of three variables, viz. poly(ethyleneimine) volume; 1-vinylimidazole volume; and applied voltage, critical to the success of the formulation. Electro-responsive drug release was determined on formulations exposed to varying environments to ascertain the optimal environment for the said desired release. A comparison method of formulation water content and swelling through gravimetric analysis was also conducted. Matrix resilience profiles were obtained as an insight to the ability of the ECH to revert to its original structure following applied stress. Response surface and contour plots were constructed for various response variables, namely electro-responsive drug release, matrix resilience and degree of swelling. The outcomes of the study demonstrated the success of electro-responsive drug release. The findings of the study can be utilized for the development of electro-responsive delivery systems of other drugs for the safer and effective drug delivery. Volumes of poly(ethyleneimine) (>2.6 mL) and 1-vinylimidazole (>0.7 mL), resulted in ideal therapeutic electro-responsive drug release (0.8 mg) for indomethacin. Lower amounts of poly(ethyleneimine) and amounts of 1-vinylimidazole ranging from 0.2 to 0.74 mL are consistent with greater than 1.6 mg release per stimulation. Swelling of <25–45% was seen.
Keywords: 1-Vinylimidazole; Bipolymeric interfacially plasticized electro-responsive hydrogel; Electro-conductive hydrogels; Poly(ethyleneimine); Semi-interpenetrating networks; Transdermal electro-activated and modulated drug release;
A novel pulsatile drug delivery system based on the physiochemical reaction between acrylic copolymer and organic acid: In vitro and in vivo evaluation by Ziwei Zhang; Xiaole Qi; Xiangbo Li; Jiayu Xing; Xuehua Zhu; Zhenghong Wu (66-73).
Multilayer-coating technology is the traditional method to achieve pulsatile drug release with the drawbacks of time consuming, more materials demanding and lack of efficiency. The purpose of this study was to design a novel pulsatile drug delivery system based on the physiochemical interaction between acrylic copolymer and organic acid with relatively simpler formulation and manufacturing process. The Enalapril Maleate (EM) pulsatile release pellets were prepared using extruding granulation, spheronization and fluid-bed coating technology. The ion-exchange experiment, hydration study and determination of glass transition temperature were conducted to explore the related drug release mechanism. Bioavailability experiment was carried out by administering the pulsatile release pellets to rats compared with marketed rapid release tablets Yisu®. An obvious 4 h lag time period and rapid drug release was observed from in vitro dissolution profiles. The release mechanism was a combination of both disassociated and undisassociated forms of succinic acid physiochemically interacting with Eudragit® RS. The AUC0-τ of the EM pulsatile pellets and the market tablets was 702.384 ± 96.891 h ng/mL and 810.817 ± 67.712 h ng/mL, while the relative bioavailability was 86.62%. These studies demonstrate this novel pulsatile release concept may be a promising strategy for oral pulsatile delivery system.
Keywords: Pulsatile pellets; Organic acid; Acrylic copolymer; Enalapril Maleate; Film coating;
Inhaled Solid Lipid Microparticles to target alveolar macrophages for tuberculosis by Eleonora Maretti; Tiziana Rossi; Moreno Bondi; Maria Antonietta Croce; Miriam Hanuskova; Eliana Leo; Francesca Sacchetti; Valentina Iannuccelli (74-82).
The goal of the work was to evaluate an anti-tubercular strategy based on breathable Solid Lipid Microparticles (SLM) to target alveolar macrophages and to increase the effectiveness of the conventional tuberculosis (TB) therapy. Rifampicin loaded SLM composed of stearic acid and sodium taurocholate were characterized for aerodynamic diameter, surface charge, physical state of the components, drug loading and release as well as drug biological activity on Bacillus subtilis strain. Moreover, SLM cytotoxicity and cell internalization ability were evaluated on murine macrophages J774 cell lines by MTT test, cytofluorimetry and confocal laser microscopy. SLM exhibited aerodynamic diameter proper to be transported up to the alveolar epithelium, negative charged surface able to promote uptake by the macrophages and preserved drug antimicrobial activity. The negligible in vitro release of rifampicin indicated the capacity of the microparticle matrix to entrap the drug preventing its spreading over the lung fluid. In vitro studies on J774 cell lines demonstrated SLM non-cytotoxicity and ability to be taken up by cell cytoplasm. The microparticulate carrier, showing features suitable for the inhaled therapy and for inducing endocytosis by alveolar macrophages, could be considered promising in a perspective of an efficacious TB inhaled therapy by means of a Dry Powder Inhaler device.
Keywords: Tuberculosis; Solid Lipid Microparticles; Rifampicin; Inhaled therapy;
Impact of in situ granulation and temperature quenching on crystal habit and micromeritic properties of ibuprofen-cationic dextran conjugate crystanules by Amos Olusegun Abioye; Adeola Kola-Mustapha; Ketan Ruparelia (83-102).
Ibuprofen was recrystallized in the presence of aqueous solution of cationic dextran derivative, Diethylaminoethyl Dextran (Ddex) using the melt-in situ granulation-crystallization technique in order to produce a stable amorphous ibuprofen–Ddex conjugates with improved morphological, micromeritic and thermo-analytical characteristics without the use of organic solvent. Ddex was used in this study because of its ability to form conjugates with various drug molecules and enhance their physicochemical characteristics and therapeutic activities. Cationic dextrans are also biocompatible and biodegradable. Mechanism of conjugation as well as the impact of conjugation on the ibuprofen crystal habit was investigated. Gaussian type normal particle size distribution was obtained and the size of the crystals in the crystanule conjugates decreased steadily, with increasing concentration of Ddex, to a minimum of 480 nm (440-folds reduction, p < 0.05, n = 20) at Ddex molar concentration of 0.01 mM. FT-IR spectra showed electrostatic interaction and hydrogen bonding between ibuprofen and Ddex which was confirmed with the 1H NMR and 13C NMR spectra. DSC curves exhibited single peaks from the binary ibuprofen–Ddex conjugate crystanules suggesting compatibility and formation of an eutectic product. The conjugate crystanules showed broad and diffuse endothermic peaks with a glass transition temperature (T g) of 58.3 and 59.14 °C at Ddex molar concentrations of 1.56 × 10−4 and 3.125 × 10−4 mM respectively confirming the existence of ibuprofen–Ddex crystanule conjugates in amorphous state. Higher concentrations of Ddex decreased T g steadily. TGA curves showed first order degradation at low molar concentrations of Ddex up to 3.125 × 10−4 mM which coincides with the critical granular concentration of the crystanules while higher concentrations exhibited second order degradation profile. This study provides the basis for the development of stable amorphous drug–polymer conjugates with potential practical application in controlled and extended drug release formulations.
Keywords: Ibuprofen–Diethylaminoethyl Dextran conjugates; In situ granulation-crystallization; Temperature quenching; Crystanules; Crystal habit; Micromeritics;
Interplay of stimuli-responsiveness, drug loading and release for a surface-engineered dendrimer delivery system by Ruihong Liu; Mingjing Sun; Xipan Liu; Aiping Fan; Zheng Wang; Yanjun Zhao (103-107).
The objectives of this study were to generate novel thermo and pH dual responsive poly(amidoamine) (PAMAM) via precise surface engineering, and investigate the interplay of dendrimer stimuli-responsiveness and the loading and release properties of a model agent, vitamin E acetate (VEAc). A higher dendrimer generation and maximized VEAc loading at elevated pH all contributed to a lower cloud point (CP) of the dendrimer–VEAc complex. The drug loading in G3.5 surface-engineered PAMAM was 22 mol/mol (pH 7.0) and 10 mol/mol (pH 5.0), which corresponded to a complex CP value at ca. 13 °C (pH 7.0) and 46 °C (pH 5.0), respectively. At physiological conditions, only less than 40% of VEAc was liberated when reaching the plateau, whilst more than 90% of VEAc was released from such system within 6 h at pH 5.0. This was due to the transition of dendrimer surface from dehydrated state to hydrated state upon pH dropping, enabling rapid drug release for therapeutic action. This smart stimuli-responsive dendritic delivery system holds promise for the efficient drug delivery to tissues with pH abnormality such as tumor.
Keywords: Dendrimers; Stimuli-responsive; Dendrimer–drug interactions; Surface-engineering; Controlled release;
Energy-based analysis of cone milling process for the comminution of roller compacted flakes by Asim Kumar Samanta; Likun Wang; Ka Yun Ng; Paul Wan Sia Heng (108-114).
Cone mill is commonly used for the milling of wet and dry agglomerates in the pharmaceutical industry as it is capable of producing milled granules with desired size characteristics. The aim of this study was to evaluate the various cone mill process parameters in terms of milling rate and energy consumption for the comminution of roller compacted flakes. A placebo formulation containing microcrystalline cellulose, lactose and magnesium stearate was used to evaluate the milling performance. Results of this study showed that higher milling rate was obtained with the combination of higher impeller speed, teethed round sidearm impeller and grater screen surface profile. Either one of the later two parameters when present in any mill setting was found to be capable of shortening the residence time of flakes inside the milling chamber, thus resulting in a higher milling rate. On the other hand, selection of appropriate screen surface profile and impeller speed was very important at lowering the effective specific energy consumption during milling. Grater screen surface profile and impeller speed between 2000 and 2400 rpm were found to act synergistically as the best combination for an energy sparing process. Impeller sidearm shape was found to have no significant effect on energy consumption.
Keywords: Roller compaction; Flakes; Cone milling; Effective specific energy; Milling rate;
Raman mapping for kinetic analysis of crystallization of amorphous drug based on distributional images by Hiroshi Ueda; Yasuo Ida; Kazunori Kadota; Yuichi Tozuka (115-122).
The feasibility of Raman mapping for understanding the crystallization mechanism of an amorphous drug was investigated using described images. The crystallization tendency of amorphous indomethacin under dry condition at 30 °C was kinetically evaluated by means of Raman mapping and X-ray powder diffraction (XRPD) with change in the calculated crystallinities. Raman images directly revealed the occurrence of particle size-dependent non-uniform crystallization; slow crystallization of large particles, but fast crystallization of small particles. Kinetic analysis by fitting to the Kolmogorov–Johnson–Mehl–Avrami equation was performed for the crystallization profiles of both Raman mapping and XRPD data. For the Raman mapping data, the distribution of large particles was characterized and examined. The kinetic parameters calculated from the whole Raman image area agreed well with those of XRPD, suggesting accurate prediction of both techniques for the entire crystallization. Raman images revealed the change in the crystallization mechanism for the focused area; the large particles showed a reduced crystallization rate constant and an increase in the dimensional crystal growth exponent. Raman mapping is an attractive tool for quantitative and kinetic investigation of the crystallization mechanism with distributional images.
Keywords: Raman mapping; Amorphous drug; Crystallization mechanism; Kinetic analysis;
An in vitro test of the efficacy of silver-containing wound dressings against Staphylococcus aureus and Pseudomonas aeruginosa in simulated wound fluid by Jawal Said; Cornelius C. Dodoo; Michael Walker; David Parsons; Paul Stapleton; Anthony E. Beezer; Simon Gaisford (123-128).
An isothermal microcalorimetric assay was used to quantify the efficacy of a silver-containing wound dressing against two common wound pathogens, Pseudomonas aeruginosa and Staphylococcus aureus. The growth patterns of the two species were unique and varied depending on the environment in which the organisms were grown. Addition of non-silver-containing dressing altered the growth kinetics while addition of silver (contained either in a dressing or as AgNO3 solution) was seen to elicit inhibition and/or kill depending on concentration. Tests were conducted in nutrient broth and simulated wound fluid. It was found that minimum inhibitory and minimum bactericidal concentration values were higher in simulated wound fluid and under anaerobic conditions. Bioavailability of silver from the wound dressing was 35% against S. aureus in nutrient broth and 68% against both species in simulated wound fluid. The data highlight the importance of developing and conducting in vitro assays in biorelevant media.
Keywords: Staphylococcus aureus; Pseudomonas aeruginosa; Isothermal calorimetry; Wound dressings; Silver, Efficacy;
Anti HIV nanoemulsion formulation: Optimization and in vitro–in vivo evaluation by Sabna Kotta; Abdul Wadood Khan; Shahid H. Ansari; Rakesh Kumar Sharma; Javed Ali (129-134).
The objective of the present work is to develop a dose adjustable nanotechnology based liquid formulation of efavirenz with improved bioavailability for HIV therapy. Nanoemulsion of efavirenz was developed using phase inversion composition method with the help of ternary phase diagram. Globule size of the o/w nanoemulsion was studied with the help of dynamic light scattering and further confirmed with TEM analysis. Optimized formulations were subjected for in vitro dissolution studies and in vivo studies were done in rats to calculate pharmacokinetics parameters and compared with efavirenz suspension. TEM results revealed that the globule size of optimized formulation was less than 30 nm. In vitro release profile showed more than 80% release within 6 h which was highly significant (p > 0.05) and pharmacokinetic studies also proved a promising in vivo absorption profile when compared to the efavirenz suspension. The developed nanoemulsion proved to be an effective dose adjustable formulation of efavirenz for pediatric HIV therapy.
Keywords: Nanoemulsion; Efavirenz; Condensation method; Phase inversion composition;
Assessing sinus aerosol deposition: Benefits of SPECT–CT imaging by Lara Leclerc; Jérémie Pourchez; Nathalie Prevot; Laurent Vecellio; Sandrine Le Guellec; Michèle Cottier; Marc Durand (135-141).
Aerosol inhalation therapy is one of the methods to treat rhinosinusitis. However the topical drug delivery to the posterior nose and paranasal sinuses shows only limited efficiency. A precise sinusal targeting remains a main challenge for aerosol treatment of sinus disorders. This paper proposes a comparative study of the nasal deposition patterns of micron and submicron particles using planar gamma-scintigraphy imaging vs. a new 3-dimensional (3D) imaging approach based on SPECT–CT measurements.Radiolabelled nebulizations have been performed on a plastinated model of human nasal cast coupled with a respiratory pump. First, the benefits provided by SPECT–CT imaging were compared with 2D gamma-scintigraphy and radioactive quantification of maxillary sinus lavage as reference for the sonic 2.8 μm aerosol sinusal deposition. Then, the impact on nasal deposition of various airborne particle sizes was assessed.The 2D methodology overestimates aerosol deposition in the maxillary sinuses by a factor 9 whereas the 3D methodology is in agreement with the maxillary sinus lavage reference methodology. Then with the SPECT–CT approach we highlighted that the higher particle size was mainly deposited in the central nasal cavity contrary to the submicron aerosol particles (33.8 ± 0.6% of total deposition for the 2.8 μm particles vs. 1 ± 0.3% for the 230 nm particles).Benefits of SPECT/CT for the assessment of radiolabelled aerosol deposition in rhinology are clearly demonstrated. This 3D methodology should be preferentially used for scintigraphic imaging of sinusal deposition in Human.
Keywords: Aerosol therapy; Aerosol deposition; SPECT/CT imaging;