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Microfluidic produced nanogels provide an alternative to standard transfection reagents for the manufacture of adeno-associated viral vectors (AAVs), with equivelant viral titres demonstrated.

Ionic gelation is commonly used to generate nanogels but often results in poor control over size and polydispersity. In this work we present a novel approach to the continuous manufacture of protein-loaded chitosan nanogels using microfluidics whereby we demonstrate high control and uniformity of the product characteristics. Specifically, a coaxial flow reactor (CFR) was employed to control the synthesis of the nanogels, comprising an inner microcapillary of internal diameter (ID) 0.595 mm and a larger outer glass tube of ID 1.6 mm. The CFR successfully facilitated the ionic gelation process via chitosan and lysozyme flowing through the inner microcapillary, while cross-linkers sodium tripolyphosphate (TPP) and 1-ethyl-2-(3-dimethylaminopropyl)-carbodiimide (EDC) flowed through the larger outer tube. In conjunction with the CFR, a four-factor three-level face-centered central composite design (CCD) was used to ascertain the relationship between various factors involved in nanogel production and their responses. Specifically, four factors including chitosan concentration, TPP concentration, flow ratio and lysozyme concentration were investigated for their effects on three responses (size, polydispersity index (PDI) and encapsulation efficiency (% EE)). A desirability function was applied to identify the optimum parameters to formulate nanogels in the CFR with ideal characteristics. Nanogels prepared using the optimal parameters were successfully produced in the nanoparticle range at 84 ± 4 nm, showing a high encapsulation efficiency of 94.6 ± 2.9% and a high monodispersity of 0.26 ± 0.01. The lysis activity of the protein lysozyme was significantly enhanced in the nanogels at 157.6% in comparison to lysozyme alone. Overall, the study has demonstrated that the CFR is a viable method for the synthesis of functional nanogels containing bioactive molecules.

Electrospun zein nanofibers have attracted interest as drug delivery systems due to their propensity for controlled drug release, flexible structure and low toxicity. However, comparatively little is known regarding the relationship between production method and fiber characteristics, both in terms of fiber architecture and protein structure. Here we use a range of imaging and spectroscopic techniques to elucidate the effects of solvent composition on zein secondary structure, fiber diameter and fiber integrity, plus we utilize the new technique of transition temperature microscopy to examine the thermal properties of the fibers. Zein nanofibers were prepared using ethanol, acetic acid and water mixes as solvents, alone and with plasticizers (polyethylene glycol, glycerol) and casein. Electrospinning was performed under controlled conditions and the products characterized using scanning electron microscopy (SEM), attenuated total reflection Fourier Transform infrared spectrometry (ATR - FTIR) and transition temperature microscopy (TTM). The choice of solvent, concentration and voltage, alongside the presence of additives (plasticizers and casein) were noted to influence both the diameter of the fibers and the tendency for bead formation. A relationship was noted between protein secondary structure and fiber architecture, with an enhanced β-sheet content, enhanced by the inclusion of casein, being associated with higher beading. In addition, thermal imaging of electrospun zein fiber mats was successfully achieved using TTM via two dimensional mapping of the softening temperatures across the spun samples, in particular demonstrating the plasticizing effects of the polyethylene glycol and glycerol.

Olanzapine is a polymorphic drug molecule that has been extensively studied, with over 60 structures reported in the Cambridge Structural Database. All anhydrous and solvated forms of olanzapine known to date contain the SC0 dimer packing motif. In this study, a new screening approach was adopted involving heat-induced forced crystallization from a polymer-based molecular dispersion of olanzapine. Simultaneous differential scanning calorimetry–powder X-ray diffraction was used to heat the amorphous dispersion and to identify a novel physical form from diffraction and heat flow data. Comparison of the diffraction data with those from a computed crystal energy landscape allowed the crystal structure to be determined. The result was the discovery of a new polymorph, form IV, which does not use the SC0 motif. Hence, while dimer formation is the dominant process that defines crystal packing for olanzapine formed from solution, it seems that molecularly dispersing the drug in a polymeric matrix permits crystall...

The orally disintegrating tablet (ODT) has shown vast potential as an alternative oral dosage form to conventional tablets wherein they can disintegrate rapidly (&le, 30 s) upon contact with saliva fluid and should have an acceptable mouthfeel as long as their weight doesn&rsquo, t exceed 500 mg. However, owing to the bitterness of several active ingredients, there is a need to find a suitable alternative to ODTs that maintains their features and can be taste-masked more simply and inexpensively. Therefore, electrospun nanofibers and solvent-cast oral dispersible films (ODFs) are used in this study as potential OD formulations for prednisolone sodium phosphate (PSP) that is commercially available as ODTs. The encapsulation efficiency (EE%) of the ODFs was higher (&asymp, 100%) compared to the nanofibers (&asymp, 87%), while the disintegration time was considerably faster for the electrospun nanofibers (&asymp, 30 s) than the solvent-cast ODFs (&asymp, 700 s). Hence, accelerated release rate of PSP from the nanofibers was obtained, due to their higher surface area and characteristic surface morphology that permitted higher wettability and thus, faster erosion. Taste-assessment study using the electronic-tongue quantified the bitterness threshold of the drug and its aversiveness concentration (2.79 mM). Therefore, a taste-masking strategy would be useful when further formulating PSP as an OD formulation.

Drug crystallization on and in the skin has been reported following application of topical or transdermal formulations. This study explored novel probe-based approaches including localized nanothermal analysis (nano-TA) and photothermal microspectroscopy (PTMS) to investigate and locate drug crystals in the stratum corneum (SC) of porcine skin following application of simple ibuprofen (IBU) formulations. We also conducted in vitro skin permeation studies and tape stripping. The detection of drug crystals in the SC on tape strips was confirmed using localized nano-TA, based on the melting temperature of IBU. The melting of IBU was also evident as indicated by a double transition and confirmed the presence of drug crystals in the SC. The single point scans of PTMS on the tape strips allowed collection of the photothermal FTIR spectra of IBU, confirming the existence of drug crystals in the skin. The combined methods also indicated that drug crystallized in the SC at a depth of ∼4-7 μm. Future studies will examine the potential of these techniques to probe crystallization of other commonly used actives in topical and transdermal formulations.

A human panel study was performed to investigate the acceptability of orodispersible electrospun and solvent cast films. 50 healthy volunteers took two drug-free samples of polyvinyl alcohol films prepared by the two methods. On a 5-point hedonic scale, the volunteers assessed the films’ perceived size, stickiness, thickness, disintegration time, thickening effect on saliva, and handling. The films manufactured by both methods were similar in their end-user acceptability. The modal values of perceived size, thickness, disintegration time, saliva thickening effect, and handling were high (4 or 5). However, for both, the stickiness mode was 2 (strongly sticky) and the only negative attribute. Both films were reported to take approximately 30 s to disintegrate completely in the mouth. Electrospun films scored similarly high to solvent cast orodispersible films in most attributes of end-user acceptability. Electrospun films were marginally preferred, with 27 out of 50 participants picking electrospinning when presented with a forced choice test of both fabrication methods. This is the first study to show that electrospinning enables the fabrication of orodispersible films that are acceptable to adult human participants in terms of handling and mouthfeel and suggests that the potential for clinical translation of such formulations is high.

Corneal abrasion is a scratch wound on the surface of the anterior segment of the eye, which can predispose a patient to corneal infection and scarring, particularly if the cut penetrates to the deep corneal layers. Here we investigate a novel approach to co-administer an anti-scarring agent and an antibiotic, both being incorporated into one dosage form so as to accelerate wound closure and to treat any associated infection. More specifically, we have used electrospun fibers as a means of incorporating the two drugs into distinct compartments via coaxial electrospinning. Samples were characterised using a range of imaging, spectroscopic and thermal methods, while an HPLC assay has been developed to allow measurement of the concentration of both drug components in both the initial fibers and on release. Fibers loaded with pirfenidone in the hydrophobic polymer, PLGA, as the outer layer and moxifloxacin in the hydrophilic polymer PVP as the inner layer were successfully prepared, with smooth and non-porous surfaces and a mean diameter of circa 630 nm. TEM image demonstrated clear distinctive layers (a core and a shell), suggesting the successful preparation of the drug-loaded coaxial fibers, supported by HPLC entrapment studies, while fluorescence microscopy confirmed the presence of the moxifloxacin within the fibers. The fibers were capable of extending the release of both drugs, hence raising the possibility of a single daily dose of the drug-loaded coaxial fibers for the treatment of corneal abrasion.

[Image: see text] Electrospinning is increasingly becoming a viable means of producing drug delivery vehicles for oral delivery, particularly as issues of manufacturing scalability are being addressed. In this study, electrospinning is explored as a taste-masking manufacturing technology for bitter drugs. The taste-masking polymer Eudragit E PO (E-EPO) was electrospun, guided by a quality by design approach. Using a design of experiment, factors influencing the production of smooth fibers were investigated. Polymer concentration, solvent composition, applied voltage, flow rate, and gap distance were the parameters examined. Of these, polymer concentration was shown to be the only statistically significant factor within the ranges studied (p-value = 0.0042). As the concentration increased, smoother fibers were formed, coupled with an increase in fiber diameter. E-EPO (35% w/v) was identified as the optimum concentration for smooth fiber production. The optimized processing conditions identified were a gap distance of 175 mm, an applied voltage of between 15 and 20 kV, and a flow rate of 1 mL/h. Using this knowledge, the production optimization of electrospun E-EPO with chlorpheniramine maleate (CPM), a bitter antihistamine drug, was explored. The addition of CPM in drug loads of 1:6 up to 1:10 CPM/E-EPO yielded smooth fibers that were electrospun under conditions similar to placebo fibers. Solid-state characterization showed CPM to be molecularly dispersed in E-EPO. An electronic tasting system, or E-tongue, indicated good taste-masking performance as compared to the equivalent physical mixtures. This study therefore describes a means of producing, optimizing, and assessing the performance of electrospun taste-masked fibers as a novel approach to the formulation of CPM and potentially other bitter drug substances.

This study describes the preparation of free films of zein with and without acetylated high amylose maize starch (HAS) and their corresponding coated tablets as a novel approach to colonic drug delivery. We hypothesise that the embedding of a digestible starch component within the inert zein would allow the film to remain intact until the large intestine is reached. Free films of zein alone and starch/zein were prepared and characterised. SEM and AFM images of film surface showed that films were morphologically inhomogeneous, particularly at lower HAS/Zein ratios; however, nanothermal analysis data suggested that these differences in appearance within the same film are not compositional differences, i.e. the systems are not phase-separated. Moreover, FT-IR could detect no molecular interaction between the two polymers. Paracetamol tablets were coated with HAS/Zein aqueous based coatings of different compositions to a TWG of 20%. Drug release from zein alone and 1:5 HAS/Zein coated tablets under upper gastrointestinal conditions (pH 1.2, pH 6.8 with pepsin and pancreatin included) was very similar (for example approximately 12% and 14% of the drug was released, respectively, after 6 hours in a sequential in vitro test), suggesting that release in this region is limited and is not influenced by the presence of HAS in the ratio to zein under study. Studies using an in vitro colon model showed that under simulated colonic conditions, the drug release was significantly (p < 0.05) more rapid from 1:5 HAS/Zein, compared to the zein alone coating formulation. These data therefore support the potential use of zein-starch mixed films for colonic targeting purposes.

The assessment of drug-polymer equilibrium solubility is of critical importance for predicting suitable loading and physical stability of solid dispersion formulations. However, quantitative measurement of this parameter is nontrivial due to the difficulties associated with ascertaining equilibrium values in systems that are prone to supersaturation and are simultaneously highly viscous, thereby slowing the equilibration process considerably; no standard methodology has yet been agreed for such measurements. In this study, we propose a new approach involving quasi-isothermal modulated temperature DSC (QiMTDSC), whereby unsaturated and supersaturated samples are held at defined temperatures and subject to a sinusoidal heating signal at a zero underpinning heating rate, thereby allowing the heat capacity of the sample to be measured as a function of time and temperature. We are not only able to ascertain whether equilibrium has been reached by monitoring the time-dependent heat capacity signal, but we can also measure solubility as a function of temperature via the absolute heat capacity values of the components. We are also able to measure the kinetics of recrystallization from the supersaturated systems. Dispersions of olanzapine in PLGA at concentrations up to 50% w/w, prepared by spray drying, were prepared and characterized using conventional and QiMTDSC as well as hot stage microscopy. The new QiMTDSC protocol was successfully able to determine olanzapine solubility in PLGA at 90 °C to be 23.1 ± 6.1% w/w, which was comparable to the values calculated using other established methods at this temperature, while a temperature/solubility profile was obtained using the method at a range of temperatures. Drug crystallization kinetics from the solid dispersions could also be modeled directly from the QiMTDSC data using the Avrami approach, thereby allowing the effect of drug loading on the rate of crystallization and the effective completion of crystallization to be investigated. Overall, an alternative protocol for measuring drug-polymer solubility has been developed and validated via comparison to established methods, the approach allowing solubility as a function of temperature, identification of equilibrium following demixing, and kinetic analysis of crystallization to be performed within one set of experiments.

Mucoadhesive delivery systems have attracted remarkable interest recently, especially for their potential to prolong dosage form resident times at sites of application such as the vagina or nasal cavity, thereby improving convenience and compliance as a result of less frequent dosage. Mucoadhesive capabilities need to be routinely quantified during the development of these systems. This is however logistically challenging due to difficulties in obtaining and preparing viable mucosa tissues for experiments. Utilizing artificial membranes as a suitable alternative for quicker and easier analyses of mucoadhesion of these systems is currently being explored. In this study, the mucoadhesive interactions between progesterone-loaded fibers (with varying carboxymethyl cellulose (CMC) content) and either artificial (cellulose acetate) or mucosa membranes are investigated by texture analysis and results across models are compared. Mucoadhesion to artificial membrane was about 10 times that of mucosa, though statistically significant ( p = 0.027) association between the 2 data sets was observed. Furthermore, a hypothesis relating fiber-mucosa interfacial roughness (and unfilled void spaces on mucosa) to mucoadhesion, deduced from some classical mucoadhesion theories, was tested to determine its validity. Points of interaction between the fiber and mucosa membrane were examined using atomic force microscopy (AFM) to determine the depths of interpenetration and unfilled voids/roughness, features crucial to mucoadhesion according to the diffusion and mechanical theories of mucoadhesion. A Kendall's tau and Goodman-Kruskal's gamma tests established a monotonic relationship between detaching forces and roughness, significant with p-values of 0.014 and 0.027, respectively. A similar relationship between CMC concentration and interfacial roughness was also confirmed. We conclude that AFM analysis of surface geometry following mucoadhesion can be explored for quantifying mucoadhesion as data from interfacial images correlates significantly with corresponding detaching forces, a well-established function of mucoadhesion.

Recent evidence has continued to support the applicability of progesterone in preventing preterm birth, hence the development of an appropriate vaginal delivery system for this drug would be of considerable interest. Here, we describe the development of progesterone-loaded bioadhesive nanofibers using pressurized gyration for potential incorporation into a vaginal insert, with a particular view to addressing the challenges of incorporating a poorly water-soluble drug into a hydrophilic nanofiber carrier. Polyethylene oxide and carboxymethyl cellulose were chosen as polymers to develop the carrier systems, based on previous evidence of their yielding mucoadhesive nanofibers using the pressurized gyration technique. The fabrication parameters such as solvent system, initial drug loading and polymer composition were varied to facilitate optimisation of fiber structure and efficiency of drug incorporation. Such studies resulted in the formation of nanofibers with satisfactory surface appearance, diameters in the region of 400 nm and loading of up to 25% progesterone. Thermal and spectroscopic analyses indicated that the drug was incorporated in a nanocrystalline state. Release from the drug-loaded fibers indicated comparable rates of progesterone dissolution to that of Cyclogest, a commercially available progesterone pessary, allowing release over a period of hours. Overall, the study has shown that pressurized gyration may produce bioadhesive progesterone-loaded nanofibers which have satisfactory loading of a poorly water-soluble drug as well as having suitable structural and release properties. The technique is also capable of producing fibers at a yield commensurate with practical applicability, hence we believe that the approach shows considerable promise for the development of progesterone dosage forms for vaginal application.

Taste assessment in an increasingly important aspect of formulation development, particularly for paediatric medications. Electronic taste sensing systems have the potential to offer a rapid, objective and safe method of taste assessment prior to the use of more costly human panels or animal models. In this study, the ability of the TS-5000Z taste sensing system to assess the taste masking efficiency of (2-hydroxypropyl)-β-cyclodextrin (HP-β-CyD) complexes with ranitidine hydrochloride was evaluated in order to explore the potential of the biosensor approach as a means of assessing taste masking by inclusion complexation. Nuclear magnetic resonance (NMR) spectroscopy and molecular docking studies were employed to identify and examine the interaction between ranitidine hydrochloride and HP-β-CyD. Taste-masking efficiencies were determined by the Euclidean distance between taste-masked formulations and the pure drug substance on a PCA score plot. The results showed that with increasing molarity of HP-β-CyD in the formulation, the distance from ranitidine hydrochloride increased, thus indicating a significant difference between the taste of the formulation and that of the pure drug. NMR studies also provided strong supporting evidence for the complexation between HP-β-CyD and ranitidine hydrochloride, with the H3' region of the former identified as the most likely binding site for the drug. Molecular docking studies suggested that the dimethylamino and diamine groups of the drug form direct hydrogen bonds with the hydroxyl oxygen atoms of HP-β-CyD, while the furan ring docks in close proximity to H3'. This study has demonstrated that the biosensor system may provide quantitative data to assess bitterness of inclusion complexes with HP-β-CyD, while spectroscopic and modelling studies may provide a mechanistic explanation for the taste masking process. This in turn suggests that there is a role for biosensor approaches in providing early screening for taste masking using inclusion complexation and that the combination with mechanistic studies may provide insights into the molecular basis of taste and taste masking.

Temperature-controlled, solvent-free centrifugal spinning may be used as a means of rapid production of amorphous solid dispersions in the form of drug-loaded sucrose microfibers. However, due to the high content of amorphous sucrose in the formulations, such microfibers may be highly hygroscopic and unstable on storage. In this study, we explore both the effects of water uptake of the microfibers and the consequences of deliberate recrystallization for the associated dissolution profiles. The stability of sucrose microfibers loaded with three selected BCS class II model drugs (itraconazole (ITZ), olanzapine (OLZ), and piroxicam (PRX)) was investigated under four different relative humidity conditions (11, 33, 53, and 75% RH) at 25 °C for 8 months, particularly focusing on the effect of the highest level of moisture (75% RH) on the morphology, size, drug distribution, physical state, and dissolution performance of microfibers. While all samples were stable at 11% RH, at 33% RH the ITZ-sucrose system showed greater resistance against devitrification compared to the OLZ- and PRX-sucrose systems. For all three samples, the freshly prepared microfibers showed enhanced dissolution and supersaturation compared to the drug alone and physical mixes; surprisingly, the dissolution advantage was largely maintained or even enhanced (in the case of ITZ) following the moisture-induced recrystallization under 75% RH. Therefore, this study suggests that the moisture-induced recrystallization process may result in considerable dissolution enhancement compared to the drug alone, while overcoming the physical stability risks associated with the amorphous state.

Hot melt extrusion has gained considerable attention as a novel technique for taste masking of bitter APIs. The aim of this study was to investigate whether hot melt extrusion could be used to develop taste masked formulations of isoniazid and also to evaluate and correlate different taste assessment methods Two polymers with different physico-chemical properties, Soluplus and Eudragit E-PO were chosen as carriers for the drug. Eudragit E-PO has already been widely used for taste masking due to its selective release properties, while Soluplus has not been studied in this regard but provides a useful comparator of a polymer that should release the drug reasonably efficiently. Polymeric formulations of isoniazid were produced with drug loadings of 20% and 30% w/w. The solid state characteristics of the formulations were assessed by differential scanning calorimetry and powder X-ray diffraction. The taste of isoniazid was assessed using the rodent Brief Access Taste Aversion (BATA) model, while formulations were assessed using the electronic tongue and dissolution under simulated oral conditions. Investigation into the drug loading effect with these two polymers showed that all Soluplus based extrudates with drug loading up to 30% w/w were fully amorphous while Eudragit E-PO based extrudates contained crystalline drug as demonstrated by both DSC and PXRD, dependent on loading. BATA testing of isoniazid gave an IC

Nanofibrous systems are attracting increasing interest as a means of drug delivery, although a significant limitation to this approach has been manufacture on a scale commensurate with dosage form production. However, recent work has suggested that nanofibers may be successfully manufactured on a suitable scale using the novel process of pressurized gyration (PG). In this study, we explore the potential of PG as a novel means of generating amorphous solid dispersions of poorly water-soluble drugs with enhanced dissolution performance. We examine the effect of increasing drug loading on fiber properties including size, surface characteristics, and the physical state of both components. Dispersions of ibuprofen in poly(vinylpyrrolidone) (PVP) were prepared (up to 50% w/w loading) and characterized using a range of imaging, thermal, diffraction, and spectroscopic techniques, while the release profiles were studied using sink and non-sink (pH 1.0) conditions. The drug was found to be dispersed on a molecular basis within the fibers; attenuated total reflection FTIR indicated evidence for a direct interaction between the drug and polymer at lower drug loading by the identification of a strong single band in the carbonyl region and amide region of ibuprofen and PVP respectively. Dissolution studies under sink conditions indicated a substantial increase in release rate, while non-sink studies showed evidence for supersaturation. It is concluded that PG presents a viable method for the production of drug-loaded nanofibers for oral administration with enhanced in vitro dissolution rate enhancement.

A one-pot single-step novel process has been developed to form microbubbles up to 250 μm in diameter using a pressurized rotating device. The microbubble diameter is shown to be a function of rotational speed and working pressure of the processing system, and a modified Rayleigh-Plesset equation has been derived to explain the bubble-forming mechanism. A parametric plot is constructed to identify a rotating speed and working pressure regime, which allows for continuous bubbling. Bare protein (lysozyme) microbubbles generated in this way exhibit a morphological change, resulting in microcapsules over a period of time. Microbubbles prepared with gold nanoparticles at the bubble surface showed greater stability over a time period and retained the same morphology. The functionalization of microbubbles with gold nanoparticles also rendered optical tunability and has promising applications in imaging, biosensing, and diagnostics.

Microthermal analysis is a recently introduced thermoanalytical technique whereby discrete regions of complex samples may be scrutinized at micron or submicron resolution. In this investigation, the novel use of the technique to study individual powder particles is described.A TA Instruments microthermal analyzer was used in local thermal analysis mode using a heating rate of 10 degrees C/s. Powder samples of crystalline ibuprofen, spray-dried salbutamol sulphate, spray-dried and crystalline trehalose, and two polymorphic forms of indometacin were studied using differential scanning calorimetry as a supportive technique as appropriate.The ibuprofen showed a probe position discontinuity corresponding to the melting point of the material. Spray-dried salbutamol sulphate showed a discontinuity corresponding to decomposition but not to the glass transition, whereas both crystalline and amorphous trehalose showed a single discontinuity corresponding to physical collapse of the material. Studies using the alpha and gamma forms of indometacin showed that the technique was able to distinguish between the two polymorphic forms.The study suggests that micro-TA may be used to assess interparticulate composition and homogeneity.

To evaluate the phase separation in itraconazole/Eudragit E100 solid dispersions prepared by hot-stage extrusion.Extrudates were prepared using a corotating twin-screw extruder at 180 degrees C. Micro-TA was used to evaluate the phase separation, where the AFM mode is used to visualize the different phases and local thermal analysis (LTA) to characterize the different phasesItraconazole formed a homogeneous mixture with Eudragit E100 with drug concentrations up to approximately 20%. Above this concentration, phase separation was observed. MTDSC revealed two Tgs and the mesophase of free glassy itraconazole. Performing micro-TA on the surface of these dispersions indicated an increase in sample roughness in the z-axis piezo signal, which could be an indication of free glassy itraconazole. However, thermal conductivity did not reveal differences between separate phases. Performing LTA, where only a small area (20 x 20 microm) is heated, showed two separate and mixed phases of itraconazole and Eudragit E100. Tip penetration in itraconazole and Eudragit E100 occurred at 332K and 383K respectively. The difference in tip penetration was explained in terms of the difference in fragility.Micro-TA makes it possible to characterize separate phases of itraconazole and Eudragit E100, thereby confirming the MTDSC results on phase separation.

The first aim of the work was to evaluate the effect of atomizer design on the properties of solid lipid microparticles produced by spray congealing. Two different air atomizers have been employed: a conventional air pressure nozzle (APN) and a recently developed atomizer (wide pneumatic nozzle, WPN). Milled theophylline and Compritol® 888ATO were used to produce microparticles at drug-to-carrier ratios of 10:90, 20:80, and 30:70 using the two atomizers. The results showed that the application of different nozzles had significant impacts on the morphology, encapsulation efficiency, and drug release behavior of the microparticles. In contrast, the characteristics of the atomizer did not influence the physicochemical properties of the microparticles as differential scanning calorimetry, Hot Stage microscopy, X-ray powder diffraction, and Fourier transform infrared spectroscopy analysis demonstrated. The drug and the lipid carrier presented in their original crystalline forms in both WPN and APN systems. A second objective of this study was to develop a novel mathematical model for describing the dynamic process of drug release from the solid lipid microparticles. For WPN microparticles the model predicted the changes of the drug release behavior with particle size and drug loading, while for APN microparticles the model fitting was not as good as for the WPN systems, confirming the influence of the atomizer on the drug release behavior. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:916–931, 2010