Long term storage of virus templated fluorescent materials for sensing applications

Wild type, mutant, and chemically modified Cowpea mosaic viruses (CPMV) were studied for long term preservation in the presence and absence of cryoprotectants. Viral complexes were reconstituted and tested via fluorescence spectroscopy and a UV/vis-based RNase assay for structural integrity. When viruses lyophilized in the absence of cryoprotectant were rehydrated and RNase treated, UV absorption increased, indicating that the capsids were damaged. The addition of trehalose during lyophilization protected capsid integrity for at least 7 weeks. Measurements of the fluorescence peak maximum of CPMV lyophilized with trehalose and reconstituted also indicate that the virus remained intact. Microarray binding assays indicated that CPMV particles chemically modified for use as a fluorescent tracer were intact and retained binding specificity after lyophilization in the presence of trehalose. Thus, we demonstrate that functionalized CPMV nanostructures can be stored for the long term, enabling their use in practical sensing applications.     

Development of a lyophilized formulation for (R,R)-formoterol (L)-tartrate

(R,R)-formoterol is a beta-agonist for inhalation. Aqueous instability suggested the need for a reconstitutable lyophilized dosage form. The objective of these studies was to devise a stable, rapid-dissolving, therapeutically compatible dosage form. The effects of diluents and residual moisture on the stability of thermally stressed formoterol formulations were investigated. Drug and various excipients (acetate, lactose, and mannitol) were lyophilized and placed in humidity chambers (0 to 90% relative humidity) at 25 to 50 degrees C. Stability was characterized by time-dependent changes using HPLC, pH, and XRD. Residual moisture were determined by Karl Fisher methods. Regression models were developed to quantify the effects of formulation and environmental variation on drug stability. Solid-state instability was observed as a function of high residual moisture and diluent type. Although the residual moisture in mannitol formulations were typically below 1%, the degradation rate (50 degrees C) varied from 2 to 10 mcg/day, which was 1.3- to 20-fold high than observed for lactose formulations under the same relative humidity conditions. At high relative humidity, the presence of acetate significantly increased the degradation rate (p < 0.04). The critical residual moisture content for lactose formulations was 3%. The amount of lactose was optimized by evaluating the degradation over the temperature range 25 to 50 degrees C. Mannitol and acetate were shown to be unsuitable excipients, and an optimal lactose amount was 50 mg for vials containing 50 mcg of drug.     

Development of a Lyophilized Formulation for (R,R)-Formoterol (L)-Tartrate

(R,R)-formoterol is a β-agonist for inhalation. Aqueous instability suggested the need for a reconstitutable lyophilized dosage form. The objective of these studies was to devise a stable, rapid-dissolving, therapeutically compatible dosage form. The effects of diluents and residual moisture on the stability of thermally stressed formoterol formulations were investigated. Drug and various excipients (acetate, lactose, and mannitol) were lyophilized and placed in humidity chambers (0 to 90% relative humidity) at 25 to 50°C. Stability was characterized by time-dependent changes using HPLC, pH, and XRD. Residual moistures were determined by Karl Fisher methods. Regression models were developed to quantify the effects of formulation and environmental variation on drug stability. Solid-state instability was observed as a function of high residual moisture and diluent type. Although the residual moistures in mannitol formulations were typically below 1%, the degradation rate (50°C) varied from 2 to 10 mcg/day, which was 1.3- to 20-fold high than observed for lactose formulations under the same relative humidity conditions. At high relative humidity, the presence of acetate significantly increased the degradation rate (p < 0.04). The critical residual moisture content for lactose formulations was 3%. The amount of lactose was optimized by evaluating the degradation over the temperature range 25 to 50°C. Mannitol and acetate were shown to be unsuitable excipients, and an optimal lactose amount was 50 mg for vials containing 50 mcg of drug.     

In vitro evaluation and in vivo performance of lyophilized gliclazide

Enhancement of the dissolution rate of the poorly water-soluble hypoglycemic agent, gliclazide, by the aid of lyophilization was investigated. Mannitol, sodium lauryl sulfate (SLS) and polyvinyl pyrrolidone (PVP-k-30) were employed in different weight ratios (43%, 56% and 64% w/w, respectively) as water-soluble excipients in the formulation. Lyophilized systems were found to exhibit extremely higher in vitro dissolution rate compared to the unprocessed drug powder. Solid state characterization of the lyophilized systems using X-ray powder diffraction, Fourier transform infrared spectroscopy and differential scanning calorimetry techniques revealed that dissolution enhancement was attributable to transformation of gliclazide from the crystalline to an amorphous state in the solid dispersion formed during the lyophilization process. The gastrointestinal absorption and hypoglycemic effect of the lyophilized gliclazide/SLS system were investigated following oral administration to Albino rabbits. C_max and area under the plasma concentration–time curve of gliclazide (AUC_0–12) after administration of the lyophilized formulations were significantly higher than those obtained after administration of the unprocessed gliclazide.     

Freeze-drying of low molecular weight poly(L-lactic acid) nanoparticles: effect of cryo- and lyoprotectants

The chemical and physical stability of polymeric nanoparticles is poor in aqueous suspensions, and the drying of these particles is often problematic. In the present study, the stability of freeze-dried low molecular weight poly(L-lactic acid) (PLA) nanoparticles was enhanced by adding glucose and/or lactose to the formulation as cryo- and lyoprotectants, respectively. Also the effect of an extra stabilizer, Tween 80, was studied. The best freeze-dried PLA nanoparticle formulations were achieved, when glucose and lactose were added in combination so that the amount of lactose was double the amount of glucose. With this combination the redispersion of high-quality nanoparticles (homogenous particle dispersion with original size and without aggregates) was achieved. The addition of Tween 80 further improved the quality of freeze-dried PLA nanoparticles by facilitating the redispersion of the lyophilized cake into optimal nanoparticles.     

Comparative and Predictive Evaluation of the Stability of Different Freeze-Dried Formulations Containing an Amorphous Moisture-Sensitive Ingredient

The stability of a moisture-sensitive drug is not only determined by its own physical state, but also by the formulation in which it is present. This paper demonstrates that decomposition of amorphous vecuronium bromide in a formulation is a function of the water activity rather than of the water content in relative or stoichiometric terms. For freeze-dried formulations this means that the disadvantageous lyophilization characteristics of glass forming excipients can have definite stabilizing, other than cryoprotective, effects. With knowledge of degradation kinetics at various water levels, moisture isotherms of the formulation and the properties of package, shelf-life of a product can be estimated.     

Physical characterization and macrophage cell uptake of mannan-coated nanoparticles

Previously, we reported on a cationic nanoparticle-based DNA vaccine delivery system engineered from warm oil-in-water microemulsion precursors. In these present studies, the feasibility of lyophilizing the nanoparticles and their thermal properties were investigated. Also, the binding and uptake of the nanoparticles by a macrophage cell line were studied. The nanoparticles (prior to pDNA coating) were freeze-dried with lactose or sucrose as cryoprotectants. The stability of lyophilized nanoparticles at room temperature was monitored and compared to that of the aqueous nanoparticle suspension. The thermal properties of the nanoparticles were investigated using differential scanning calorimetry (DSC). The nanoparticles, coated or uncoated with mannan as a ligand, were incubated with a mannose receptor positive (MR+) mouse macrophage cell line (J774E), at either 4°C or 37°C to study the binding and uptake of the nanoparticles by the cells. It was found that lactose or sucrose (1-5%, w/v) was required for successful lyophilization of the nanoparticles. After 4 months of storage, the size of lyophilized nanoparticles did not significantly increase while those in aqueous suspension grew by over 900%. Unlike its individual components, emulsifying wax (m.p., ~55°C) and hexadecyltrimethyl ammonium bromide, the nanoparticles showed a melting point of ~90°C. Moreover, the DSC profile of the nanoparticles was different from that of the physical mixture of emulsifying wax and CTAB. After 1 hour incubation at 37°C, the uptake of mannan-coated nanoparticles was 50% higher than that of the uncoated nanoparticles. At 4°C and after one hour, the binding of the mannan-coated nanoparticles by J774E was over 2-fold higher than that of the uncoated nanoparticles. This increase in J774E binding could be abolished by preincubating the cells with free mannan, suggesting that the binding and uptake were receptor-mediated. In conclusion, the nanoparticles were lyophilizable, and lyophilization was shown to enhance the stability of the nanoparticles. DSC provided evidence that the nanoparticles were not a physical mixture of their individual components. Finally, cell binding and uptake studies demonstrated that the nanoparticles have potential application for cell-specific targeting.     

LEA蛋白特征片段及海藻糖对热敏性蛋白药物胰岛素冻干的协同保护研究

热敏性蛋白药物胰岛素的热稳定性较差,极易受制备方式和保存条件等影响而失活。故本研究分别利用高效液相色谱（HPLC）测定冻干样品中胰岛素的效价和差示扫描量热仪（DSC）测定冻干样品的玻璃化转变温度等重要参数,来研究胚胎发育晚期富集蛋白特征片段（LEA-motif, LEAM）和海藻糖冻干保护剂对胰岛素冻干保护效果的影响。冻干实验表明,两种保护剂均对胰岛素的活性具有保护效果,且LEAM的活性保护效果优于海藻糖。在效价和热稳定性方面,LEAM保护的胰岛素冻干品均高于海藻糖保护的胰岛素冻干样品。更为重要的是,两种保护剂协同保护时,少量海藻糖对于LEAM的保护特性具有增效作用。在冻干过程中,可有效提升药物玻璃态的稳定性,防止热致变性失活。由此可见,这种LEAM和海藻糖保护剂复合保护方法有望也可以应用在热敏性蛋白药物冻干粉针制备过程以保护药物活性。     

Physical Characterization and Macrophage Cell Uptake of Mannan-Coated Nanoparticles

Abstract

Previously, we reported on a cationic nanoparticle-based DNA vaccine delivery system engineered from warm oil-in-water microemulsion precursors. In these present studies, the feasibility of lyophilizing the nanoparticles and their thermal properties were investigated. Also, the binding and uptake of the nanoparticles by a macrophage cell line were studied. The nanoparticles (prior to pDNA coating) were freeze-dried with lactose or sucrose as cryoprotectants. The stability of lyophilized nanoparticles at room temperature was monitored and compared to that of the aqueous nanoparticle suspension. The thermal properties of the nanoparticles were investigated using differential scanning calorimetry (DSC). The nanoparticles, coated or uncoated with mannan as a ligand, were incubated with a mannose receptor positive (MR+) mouse macrophage cell line (J774E), at either 4°C or 37°C to study the binding and uptake of the nanoparticles by the cells. It was found that lactose or sucrose (1–5%, w/v) was required for successful lyophilization of the nanoparticles. After 4 months of storage, the size of lyophilized nanoparticles did not significantly increase while those in aqueous suspension grew by over 900%. Unlike its individual components, emulsifying wax (m.p., ?55°C) and hexadecyltrimethyl ammonium bromide, the nanoparticles showed a melting point of ?90°C. Moreover, the DSC profile of the nanoparticles was different from that of the physical mixture of emulsifying wax and CTAB. After 1 hour incubation at 37°C, the uptake of mannan-coated nanoparticles was 50% higher than that of the uncoated nanoparticles. At 4°C and after one hour, the binding of the mannan-coated nanoparticles by J774E was over 2-fold higher than that of the uncoated nanoparticles. This increase in J774E binding could be abolished by preincubating the cells with free mannan, suggesting that the binding and uptake were receptor-mediated. In conclusion, the nanoparticles were lyophilizable, and lyophilization was shown to enhance the stability of the nanoparticles. DSC provided evidence that the nanoparticles were not a physical mixture of their individual components. Finally, cell binding and uptake studies demonstrated that the nanoparticles have potential application for cell-specific targeting.     

Comparative and Predictive Evaluation of the Stability of Different Freeze-Dried Formulations Containing an Amorphous Moisture-Sensitive Ingredient

Abstract

The stability of a moisture-sensitive drug is not only determined by its own physical state, but also by the formulation in which it is present. This paper demonstrates that decomposition of amorphous vecuronium bromide in a formulation is a function of the water activity rather than of the water content in relative or stoichiometric terms. For freeze-dried formulations this means that the disadvantageous lyophilization characteristics of glass forming excipients can have definite stabilizing, other than cryoprotective, effects. With knowledge of degradation kinetics at various water levels, moisture isotherms of the formulation and the properties of package, shelf-life of a product can be estimated.     

Formulation for a novel inhaled peptide therapeutic for idiopathic pulmonary fibrosis

A caveolin-1 scaffolding domain, CSP7, is a newly developed peptide for the treatment of idiopathic pulmonary fibrosis. To develop a CSP7 formulation for further use we have obtained, characterized and compared a number of lyophilized formulations of CSP7 trifluoroacetate with DPBS and in combination with excipients (mannitol and lactose at molar ratios 1:5, 70 and 140). CSP7 trifluoroacetate was stable (>95%) in solution at 5 and 25?°C for up to 48?h and tolerated at least 5 freeze/thaw cycles. Lyophilized cakes of CSP7 trifluoroacetate with excipients were stable (>96%) for up to 4?weeks at room temperature (RT), and retained more than 98% of the CSP7 trifluoroacetate in the solution at 8?h after reconstitution at RT. The lyophilized CSP7 formulations were stable for up to 10?months at 5?°C protected from moisture. Exposure of the lyophilized cakes of CSP7 to 75% relative humidity (RH) resulted in an increase in the absorbed moisture, promoted crystallization of the excipients and induced reversible formation of CSP7 aggregates. Increased molar ratio of mannitol slightly affected formation of the aggregates. In contrast, lactose significantly decreased (up to 20 times) aggregate formation with apparent saturation at the molar ratio of 1:70. The possible mechanisms of stabilization of CSP7 trifluoroacetate in solid state by lactose include physical state of the bulking agent and the interactions between lactose and CSP7 trifluoroacetate (e.g. formation of a Schiff base with the N-terminal amino group of CSP7). Finally, CSP7 trifluoroacetate exhibited excellent stability during nebulization of formulations containing mannitol or lactose.     

Optimization of the lyophilization process for long-term stability of solid-lipid nanoparticles

Objectives: To optimize a lyophilization protocol for solid-lipid nanoparticles (SLNs) loaded with dexamethasone palmitate (Dex-P) and to compare the long-term stability of lyophilized SLNs and aqueous SLN suspensions at two storage conditions. Materials and Methods: The effect of various parameters of the lyophilization process on SLN redispersibility was evaluated. A three month stability study was conducted to compare changes in the particle size and drug loading of lyophilized SLNs with SLNs stored as aqueous suspensions at either 4°C or 25°C/60% relative humidity (RH). Results and Discussion: Of nine possible lyoprotectants tested, sucrose was shown to be the most efficient at achieving SLN redispersibility. Higher freezing temperatures, slower freezing rates, and longer secondary drying times were also shown to be beneficial. Loading of the SLNs with Dex-P led to slightly larger particle size and polydispersity index increases, but both parameters remained within an acceptable range. Drug loading and particle shape were maintained following lyophilization, and no large aggregates were detected. During the stability study, significant growth and drug loss were observed for aqueous SLN suspensions stored at 25°C/60% RH. In comparison, lyophilized SLNs stored at 4°C exhibited a consistent particle size and showed <20% drug loss. Other storage conditions led to intermediate results. Conclusions: A lyophilization protocol was developed that allowed SLNs to be reconstituted with minimal changes in their physicochemical properties. During a three month period, lyophilized SLNs stored at 4°C exhibited the greatest stability, showing no change in the particle size and a minimal reduction in drug retention.     

Physicochemical Stability of Crystalline Sugars and Their Spray-Dried Forms: Dependence upon Relative Humidity and Suitability for Use in Powder Inhalers

Abstract

Lactose, trehalose, sucrose, and mannitol were purchased in crystalline form and fractionated by sieving. Coarse (125-212 µm) and fine (44-74 µm) free-flowing fractions were selected as typical of drug carriers in dry-powder inhalers. In addition, one batch of each sugar was spray-dried to form a respirable powder (> 50% [w/w], < 5 µm). Both fractions and the spray-dried powders were characterized before and after storage for 30 days at < 23%, 23%, 52%, 75% and 93% relative humidity (RH) at 25°C. Moisture uptake was determined by thermogravimetric analysis (TGA) validated by Karl Fischer titration. Sieve fractions (before storage at different RHs) and spray-dried materials (before and after storage) were further characterized by differential scanning calorimetry (DSC) and x-ray powder diffraction (XRPD). All crystalline sieve fractions (except sucrose at 93% RH) were stable at 25°C and showed insignificant moisture uptake when exposed to each relative humidity for 30 days. Sucrose dissolved in sorbed moisture at 93% RH. Spray-dried lactose, sucrose, and trehalose, which were collected in the amorphous form, showed moisture uptake, without recrystallization, when held for 30 days at 23% RH. These sugars recrystallized as sintered masses and became undispersible at ≥ 52% RH. Spray-dried mannitol was apparently 100% crystalline when collected directly from the spray-dryer; it did not show humidity-induced changes.

The physicochemical behavior of each sugar form is discussed as it relates to the sugar's suitability as a powder-inhaler excipient, with both conventional and protein drugs.     

Optimization of the formulation and characterization of the physicochemical properties of the novel platelet-activating factor receptor antagonist E5880

The injectable formulation of E5880, a novel platelet-activating factor (PAF) receptor antagonist, was determined from the study of pH stability, the selection of excipient, and the relationship between moisture and stability. The physicochemical properties of E5880 in the optimized formulation (0.6 mg/ml of E5880, 0.1% [4.8 mM] citric acid, 10% lactose, pH 2.8) were characterized. The critical micelle concentration of E5880 in the buffer was 0.1 mg/ml, and the structure was of spherical micelles. The micellar size was 5.6 nm and did not change before and after lyophilization and storage. The number of the molecules per micelle was 40. The micropolarity around the hydrocarbon region of the micelle was similar to that of butanol.     

Optimization of the Formulation and Characterization of the Physicochemical Properties of the Novel Platelet-Activating Factor Receptor Antagonist E5880

The injectable formulation of E5880, a novel platelet-activating factor (PAF) receptor antagonist, was determined from the study of pH stability, the selection of excipient, and the relationship between moisture and stability. The physicochemical properties of E5880 in the optimized formulation (0.6 mg/ml of E5880, 0.1% [4.8 mM] citric acid, 10% lactose, pH 2.8) were characterized. The critical micelle concentration of E5880 in the buffer was 0.1 mg/ml, and the structure was of spherical micelles. The micellar size was 5.6 nm and did not change before and after lyophilization and storage. The number of the molecules per micelle was 40. The micropolarity around the hydrocarbon region of the micelle was similar to that of butanol.     

Optimization of the lyophilization process for long-term stability of solid–lipid nanoparticles

Objectives: To optimize a lyophilization protocol for solid–lipid nanoparticles (SLNs) loaded with dexamethasone palmitate (Dex-P) and to compare the long-term stability of lyophilized SLNs and aqueous SLN suspensions at two storage conditions.

Materials and Methods: The effect of various parameters of the lyophilization process on SLN redispersibility was evaluated. A three month stability study was conducted to compare changes in the particle size and drug loading of lyophilized SLNs with SLNs stored as aqueous suspensions at either 4°C or 25°C/60% relative humidity (RH).

Results and Discussion: Of nine possible lyoprotectants tested, sucrose was shown to be the most efficient at achieving SLN redispersibility. Higher freezing temperatures, slower freezing rates, and longer secondary drying times were also shown to be beneficial. Loading of the SLNs with Dex-P led to slightly larger particle size and polydispersity index increases, but both parameters remained within an acceptable range. Drug loading and particle shape were maintained following lyophilization, and no large aggregates were detected. During the stability study, significant growth and drug loss were observed for aqueous SLN suspensions stored at 25°C/60% RH. In comparison, lyophilized SLNs stored at 4°C exhibited a consistent particle size and showed <20% drug loss. Other storage conditions led to intermediate results.

Conclusions: A lyophilization protocol was developed that allowed SLNs to be reconstituted with minimal changes in their physicochemical properties. During a three month period, lyophilized SLNs stored at 4°C exhibited the greatest stability, showing no change in the particle size and a minimal reduction in drug retention.     

Preparation, characterization, and stability of liposome-based formulations of mitoxantrone

The preparation, characterization, and stability of lyophilized liposome-based formulation of mitoxantrone was investigated. Mitoxantrone was entrapped inside small, unilamellar liposomes composed of dioleoylphosphocholine (DOPC), cholesterol, and cardiolipin. The mean vesicle size and drug entrapment efficiency of the liposomes were ~ 150 nm and ~ 99%, respectively. Less than 1% of drug was lost and mean vesicle size remained unchanged after sterile filtration. The pre-lyophilized (pre-lyo) formulations were characterized by a differential scanning calorimetric (DSC) method. Results showed that the glass transition temperatures (Tg') increased as the molar ratios of sucrose:lipid and trehalose:lipid in the formulations were increased. The maximum Tg' of the pre-lyo formulations containing 10:1 sucrose:lipid and trehalose:lipid molar ratios were - 37°C and - 41°C, respectively. After reconstitution of the lyophilized cake of the sucrose-containing formulation, the mean vesicle size was comparable to pre-lyo liposome size. In vitro release studies showed that less than 2% of mitoxantrone was released after an extensive dialysis against phosphate buffered saline (PBS) at 37°C, indicating that the mitoxantrone was highly associated and retained inside the liposomes. Short-term stability studies of the sucrose-containing formulations revealed that the reconstituted and eight-fold diluted formulations were stable for up to 8 hours at room temperature. Long-term stability studies of lyophilized liposomal mitoxantrone showed that the lyophilized formulation was stable for up to 13 months after storage at refrigerated condition.     

Preparation and evaluation of lyophilized liposome-encapsulated bufadienolides

Objective: The objective of this study was to prepare bufadienolides-loaded liposome (BU-lipo). Methods: The BU-lipo was prepared by a thin-film hydration method involving sonication and lyophilization procedures. The lyophilized BU-lipo was characterized with regard to the appearance and particle size by scanning electron microscopy, transmission electron microscopy, and photon correlation spectroscopy. The entrapment efficiency (EE) of BU-lipo was evaluated by the microdialysis technique. Results: In the optimal formulation, Lipoid E-80® and the mass ratio of cholesterol to lipid were fixed at 1.25% and 0.05. The media diameters of BU-lipo before and after lyophilization were about 100 nm, and the EEs of bufalin (B), cinobufagin (C), and resibufogenin (R) were 86.5%, 90.0%, and 92.1%, respectively. In the EE study, the probe recoveries of B, C, and R were 21.53?±?1.14%, 19.49?±?1.34%, and 20.19?±?1.25%, respectively, at a flow rate of 4 μL/min by the gain method. The EE of BU-lipo evaluated by microdialysis and ultrafiltration were equivalent. Conclusion: The lyophilized BU-lipo contained trehalose (10%) was stable up to 6 months in a desiccator under 2ºC–8ºC. The microdialysis technique has a wide application perspective in the investigation of the free-drug concentration of microcarrier systems.     

Factors influencing the properties and the stability of spray-dried Sennae fructus extracts

Objective: The objective of this study was to characterize the properties of aqueous Sennae fructus extracts prepared by spray-drying at varying process conditions.

Significance: From an industrial point of view it is essential to develop a formulation which has a constant quality over the whole period of its specified shelf-life.

Method: Sennae fructus extracts were spray-dried with different atomizing gas pressures, pump feed rates, and inlet temperatures. The extracts were analyzed for their physical properties and stored at accelerated conditions. Sennoside degradation was monitored by HPLC analysis.

Results: An increase of the atomizing gas pressure had the most pronounced influence on the decrease of moisture content and particle size. An increase of the inlet temperature led to a decrease of moisture content and particle density, as well as an increase of smooth particle amount. An increase in the pump feed rate, increased the moisture content and resulted in stable hollow spheres. The different conditions also led to smooth or wrinkled particle surfaces, and to golfball, donut, and shard particle shapes. The chemical stability of the sennosides differed from each other after storage. Stability-reducing factors were the moisture content of the samples and their hygroscopicities, as well as different particle morphologies. These factors were influenced by the inlet temperature of the spray-drying process. High inlet temperatures led to a positive influence on dryness and particle morphology and therefore on the stability of the sennosides.

Conclusions: Variation of the process conditions affected the resulting particle properties and their storage stability of Sennae fructus extract.     

Formulation of olanzapine nanosuspension based orally disintegrating tablets (ODT); comparative evaluation of lyophilization and electrospraying process as solidification techniques

Olanzapine (OLAN) as an antipsychotic agent has shown its potential in effective management of psychotic disorders however its use is limited because of its poor water solubility. The aim of present work was to improve solubility of OLAN by developing a stable nanocrystal based orally disintegrating tablets (ODTs), using hyperomellose as potential stabilizer. Comparative evaluation of electrospraying and lyophilization as solidification techniques was carried out to assess its effect on solid state properties of OLAN nanocrystals before transformation to ODTs.OLAN Nanosuspension was developed using antisolvent precipitation method and exhibited particle size, polydispersity index and zetapotential value of 223.1?±?1.5?nm, 0.105?±?0.4 and ?17.9?±?3.5?mV respectively. Solid powders obtained from both the solidification techniques were compared in terms of size after re-dispersion, particle morphology, surface area, pore volume and solid state of drug present. Subsequently ODTs were prepared from these powders with needful excipients and % amount dissolved was evaluated. Rate of dispersion was found to be higher for ODTs prepared using lyophilized powder (～84% in 5?min) while other characterization parameters were comparatively similar. Overall, Lyophilization resulted in powders with better bulk level properties in comparison to electrospraying process.