Formulation, quality control and shelf life of the experimental cytostatic drug cyclopentenyl cytosine

This paper describes the formulation and quality control of an aqueous sterilized formulation of the experimental cytostatic drug cyclopentenyl cytosine (CPEC) to be used in Phase I/II clinical trials. The raw drug substance was extensively tested. A High Pressure Liquid Chromotography (HPLC) method was validated for the quality control of the formulated product. The aqueous formulation was found to be stable for at least 2 years at 2-8°C. Sterilization (15 min at 121°C) showed no influence on drug stability. The results show that CPEC can be formulated in an aqueous solution. The described HPLC method is a useful tool in the pharmaceutical quality control.     

Pharmaceutical development of an amorphous solid dispersion formulation of elacridar hydrochloride for proof-of-concept clinical studies

Objective: A novel tablet formulation containing an amorphous solid dispersion (ASD) of elacridar hydrochloride was developed with the purpose to resolve the drug’s low solubility in water and to conduct proof-of-concept clinical studies.

Significance: Elacridar is highly demanded for proof-of-concept clinical trials that study the drug’s suitability to boost brain penetration and bioavailability of numerous anticancer agents. Previously, clinical trials with elacridar were performed with a tablet containing elacridar hydrochloride. However, this tablet formulation resulted in poor and unpredictable absorption which was caused by the low aqueous solubility of elacridar hydrochloride.

Methods: Twenty four different ASDs were produced and dissolution was compared to crystalline elacridar hydrochloride and a crystalline physical mixture. The formulation with highest dissolution was characterized for amorphicity. Subsequently, a tablet was developed and monitored for chemical/physical stability for 12 months at +15–25?°C, +2–8?°C and ?20?°C.

Results: The ASD powder was composed of freeze dried elacridar hydrochloride–povidone K30–sodium dodecyl sulfate (1:6:1, w/w/w), appeared fully amorphous and resulted in complete dissolution whereas crystalline elacridar hydrochloride resulted in only 1% dissolution. The ASD tablets contained 25?mg elacridar hydrochloride and were stable for at least 12 months at –20?°C.

Conclusions: The ASD tablet was considered feasible for proof-of-concept clinical studies and is now used as such.     

Enhanced stability and permeation potential of nanoemulsion containing sefsol-218 oil for topical delivery of amphotericin B

Aim: To characterize the enhanced stability and permeation potential of amphotericin B nanoemulsion comprising sefsol-218 oil at varying pH and temperature of aqueous continuous phase.

Methodology: Several batches of amphotericin B loaded nanoemulsion were prepared and evaluated for their physical and chemical stability at different pH and temperature. Also, a comparative study of ex vivo drug permeation across the albino rat skin was investigated with commercial Fungisome® and drug solution at 37?°C for 24?h. The extent of drug penetrated through the rat skin was thereby evaluated using the confocal laser scanning microscopy (CLSM).

Results and conclusions: The optimized nanoemulsion demonstrated the highest flux rate 17.85?±?0.5?µg/cm²/h than drug solution (5.37?±?0.01?µg/cm²/h) and Fungisome® (7.97?±?0.01?µg/cm²/h). Ex vivo drug penetration mechanism from the developed formulations at pH 6.8 and pH 7.4 of aqueous phase pH using the CLSM revealed enhanced penetration. Ex vivo drug penetration studies of developed formulation comprising of CLSM revealed enhanced penetration in aqueous phase at pH 6.8 and 7.4. The aggregation behavior of nanoemulsion at both the pH was found to be minimum and non-nephrotoxic. The stability of amphotericin B was obtained in terms of pH, optical density, globular size, polydispersity index and zeta potential value at different temperature for 90 days. The slowest drug degradation was observed in aqueous phase at pH 7.4 with shelf life 20.03-folds higher when stored at 4?°C (3.8 years) and 5-fold higher at 25?°C (0.951 years) than at 40?°C. The combined results suggested that nanoemulsion may hold an alternative for enhanced and sustained topical delivery system for amphotericin B.     

Development and physicochemical characterization of clindamycin resinate for taste masking in pediatrics

Purpose: To evaluate the physicochemical characteristics of clindamycin HCl in a complex form (resinate) with ion exchange resin (IER) (Amberlite IRP69).

Methods: Drug–resin complex was prepared by simple aqueous binding method. Drug binding study was carried out at different drug and resin concentrations. Several physicochemical characterization studies were conducted to evaluate the resinate complex. These studies included flow properties, in vitro drug release in SGF and SIF, DSC, TGA, mass spectroscopy and XPRD evaluations. In addition, stability study of resinate complex was conducted at 25?and 40?°C for up to 1 month.

Results: Clindamycin and Amberlite IRP69 have formed a complex (resinate) and have shown good flow properties, good thermal properties and chemical stability (short term over 4 weeks) at 25 and 40?°C. Clindamycin release profiles from resinate in SGF and SIF have shown immediate release characteristics and release in simulated saliva has shown dependence on water volume.

Conclusion: The clindamycin stable complex with IER (Amberlite IRP69) has the potential for further development as a compatible pediatric liquid formulation (suspension) or a fast disintegrating tablet.     

Polymorphism and drug release behavior of spray-dried microcapsules of sulfamethoxazole with polysaccharide gum and colloidal silica

Abstract

Sulfamethoxazole microcapsules with polysaccharide gum, i.e. xanthan gum and guar gum, were prepared by employing a spray drying technique. The aqueous or the ammonium hydroxide solution of the gum containing the drug with or without colloidal silica was atomized with a centrifugal wheel atomizer rotated at 40000 rpm into a drying chamber held at 140±10°C. By formulation with colloidal silica, particle size of the resultant product increased, leading to improve the flowability and packability for the tableting. Polymorphic sulfamethoxazole mixture of Form I, II and III was produced in the formulation with cellulose acetate     

Enhancing the Bioavailability of Cyclosporine A Using Solid Dispersion Containing Polyoxyethylene (40) Stearate

ABSTRACT

Solid dispersion containing polyoxyethylene (40) stearate and cyclosporine A was prepared by solvent-melt method and characterized using differential scanning calorimetry, powder X-ray diffraction, and Infrared Fourier Transform Spectroscopy (FTIR). Dissolution of the drug from solid dispersion was dramatically enhanced compared to that from the drug powder alone and physical mixture. In vivo oral bioavailability of cyclosporine A from the solid dispersion in Wistar rats was comparable to that from a commercial product, Sandimmun Neoral® (P > 0.05). The formulation is stable up to six months under 30°C/RH60% and one year at 25°C/RH 60% when packed in aluminum-polyethylene laminated bags.     

Design and evaluation of mucoadhesive vaginal tablets of tenofovir disoproxil fumarate for pre-exposure prophylaxis of HIV

Objective: To design and evaluate novel, feasible, safe, mucoadhesive intravaginal tablets of tenofovir disoproxil fumarate (TDF).

Significance: It may provide pre-exposure prophylaxis for women against HIV.

Methods: TDF intravaginal tablets were formulated employing poylvinylpyrrolidone (PVP) as the matrix forming polymer and various mucoadhesive polymers such as carbopol 934, 940, chitosan, and sodium carboxymethylcellulose (SCMC). Wet granulation was used. The evaluation involved testing drug-excipient compatibility, precompression parameters such as percentage yield, bulk density and tapped density of the granules, Carr’s index, Hausner ratio, angle of repose, post compression parameters such as color, shape, physical dimensions, weight variation, hardness, friability, swelling index, assay, in vitro dissolution study and ex vivo mucoadhesion studies.

Results: Based on in vitro evaluation, C1 was selected as the best formulation and evaluated further for release kinetics, curve fitting analysis, absorption studies using liquid chromatography-mass spectrometry (LC-MS) technique and histopathological assessment in female Sprague–Dawley rats. C1 followed Higuchi model kinetics. Accelerated stability study was as per ICH guidelines by keeping C1 at 40?±?2?°C and 75?±?5% RH for six months.

Conclusions: C1 was selected as the best formulation due to better swelling index (65.93% at 24?h), prolonged release of 100.62% cumulative drug release (CDR) at 24?h, superior mucoadhesion force (35.93?×?10² dynes/cm²) and retention time (16?h). The study revealed that C1 remained stable for six months. C1 showed nil systemic absorption which is desirable and according to histopathological study, C1, exhibited minimal damage on the rat vaginal epithelium indicating safety.     

Study on the rate of decomposition of amoxicillin in solid state using high-performance liquid chromatography

Abstract

Amoxicillin sodium salt degradation in solid state relies on a sequential reaction consisting of two pseudo-first-order processes. Amoxicillin trihydrate, now used in pharmaceutical formulations, is significantly more stable than sodium amoxicillin. It degrades according to Prout-Tompkins model. We studied the stability of amoxicillin at temperatures of 37°, 50°, 80°, 90°, 100° y 110° C. HPLC was chosen as the analytical method. Amoxicillin and its decomposition products are separated by reversed-phase (C18) HPLC with gradient elution.     

In Vitro Drug Release from Matrix Tablets Containing a Silicone Elastomer Latex

Abstract

A silicone elastomer latex was evaluated as a wet-granulating agent in preparing controlled release matrix tablets containing a water soluble active ingredient. A one-half fractional factorial statistical design was used to investigate the effect of five different formulation and non-formulation variables on the in vitro release characteristics of the drug from the matrix tablets. Tablets containing a high percent of fumed colloidal silica exhibited a faster drug release rate. A high drug to polymer ratio in the tablets was also shown to result in a faster release of the drug. Granules dried at a higher temperature (80°C vs. 60°C) produced tablets with a slower drug release rate. The release of the drug was shown to be pH dependent. A higher drug release rate was obtained in a dissolution medium with a lower pH (1.2 vs. 6.8).     

Evaluation of Cholecystokinin (CCK-8) Peptide Thermal Stability for Use as Radiopharmaceutical by Means Isothermal and Nonisothermal Approaches

ABSTRACT

The purpose of this research was to study thethermal stability of cholecystokinin octapeptide (CCK-8) in aqueous solution at pH 12 and ionic strength 0.01M, which were kept as constants, by using isothermal and nonisothermal methods.

The isothermal decomposition of CCK-8 was investigated as a function of temperature (40°C to 70°C). Nonisothermal stability studies were performed using a linear increasing temperature program. Two different nonisothermal studies were carried out at 0.25°K and 0.5°K per hour, and the temperature interval varied from 40°C to 82°C.

The degradation of CCK-8 followed first-order kinetics, obeying the Arrhenius equation in the experimental temperature range. This indicated that the degradation mechanism of CCK-8 could be the equal within the temperature range studied. The nonisothermal approach resulted in activation energy (Ea) and shelf-life (t_90%) values that agree well with those obtained by the isothermal method. The level of uncertainty in the estimates of t_90% and Ea values is determined mainly by the extent of drug degradation and temperature change during the experiment. Therefore, nonisothermal experiments save time, labor and materials (i.e. the amount of drugs necessary to conduct the experiment) compared to the classic isothermal experiments, if they are performed using a suitable experimental design and a precise analytical method.     

Absorption of Thyrotropin-Releasing Hormone in Rats Using a Mucoadhesive Buccal Patch

Abstract

Mucoadhesive buccal patches were evaluated in vitro and in vivo using rats for release of thyrotropin-releasing homne (TRH). TRH (10% w/w) was incorporated into mucoadhesive buccal patches that were custom coformulated with silicone and organic polymers (Dow Coming, Midland, MI) and its release profile was characterized in vitro using a modified Franz diffusion cell. TRH released into pH = 7.0 phosphate buffered saline at 37°C under sink conditions was detected using high-performance liquid chromatography (HPLC). Release of TRH in vitro from the buccal patches was rapid during the first 2 hr, with 51% of the total amount of TRH incolporated into the patches released after 24 hr. HPLC analysis indicated that TRH extracted from buccal patches thermally stressed at 40°, 55°, and 70°C showed negligible degradation after 6 months. In contrast, an aqueous TRH solution stored at 70°C showed degradation of TRH as soon as 10 days following incubation at this temperature. TRH patches placed on the buccal mucosa of anesthetized rats demonstrated rapid stimulation and release of thyroid-stimulating hormone (TSH) from the anterior pituitary. Thirty minutes after patch application, plasma concentrations of TSH fluctuated but remained approximately 4–to 7-fold greater than baseline (prior to patch application) TSH concentrations. Therefore, this preliminary study has demonstrated that physiologically active TRH was released from the TRH mucoadhesive buccal patches and systemically absorbed. Thus, the TRH mucoadhesive buccal patches may represent a convenient delivery system for therapeutic peptides.     

Novel oral amphotericin B formulation (iCo-010) remains highly effective against murine systemic candidiasis following exposure to tropical temperature

Purpose: To evaluate the antifungal activity of amphotericin B (AmB) in a mouse model of systemic candidiasis following administration of a novel oral AmB formulation (iCo-010) that has been pre-exposed to tropical temperatures.

Methods: Amphotericin B (AmB) was prepared as a 5?mg/mL dispersion in a mixture of Peceol, Gelucire 44/14 and VitE-TPGS 2,3 (iCo-010). The formulation was protected from light and incubated in a sealed container at 43?°C for 60 days. Mice infected with Candida albicans were treated with either iCo-010 formulation pre-incubated at 43?°C for 60 days or freshly prepared iCo-010 formulation at doses of 5, 10 and 20?mg/kg once daily for five consecutive days. Single intravenous 5?mg/kg dose of AmBisome® was used as a positive control group. Seven days following the last dose, the kidney, liver, spleen, lung, heart and brain were removed and the number of colony forming units (CFUs) was determined as a measure of tissue fungal load. In addition, the concentration of AmB within each tissue was determined using high performance liquid chromatography (HPLC).

Results: There were no significant differences in the reduction of CFUs and the concentration of AmB recovered in all organs at all iCo-010 doses tested between the freshly prepared iCo-010 formulation compared to the formulation that was incubated at 43?°C for 60 days.

Conclusions: A novel oral AmB formulation, iCo-010, incubated at 43?°C for 60 days to simulate the exposure of the formulation to tropical temperatures remained highly effective against murine systemic candidiasis.     

The MiniWiD-COATER: II. Comparison of acid resistance of enteric-coated bisacodyl pellets coated with different polymers

Abstract

Neutral pellets were loaded with bisacodyl and enteric-coated with hydroxypropyl methylcellulose acetate succinate (HPMCAS), carboxymethyl ethylcellulose (CMEC), cellulose acetate trimellitate (CAT), and poly(ethylacrylate, methacrylic acid) (Eudragit L 30 D) in a miniature fluid-bed pan coater called MiniWiD. Gastric juice resistance was tested by dissolution using USP Apparatus 2 (paddle) in 0.1 N hydrochloric acid under sink conditions over 6 hours. As a measure of enteric coating quality the USP specifications were used meaning that no more than 10 % of the drug should be released within 2 hours.

Organic-solvent based films of HPMCAS, CMEC and CAT at a coating level of 18 to 25 % provided gastroresistance for more than 6 hours. Aqueous suspensions of HPMCAS and CMEC as well as the ammonium salt aqueous solutions of CAT produced films with a short gastroresistance of below 0.6 hours. By doubling the coating level of water-based HPMCSD films the protection was prolonged to 3.4 h.

Enteric coatings were obtained from all aqueous latex dispersions of Eudragit L 30 D at a coating level of 24 %. The alteration of coating temperature between 25 and 45 °C had no significant effect on the release rates, whereas the variation of type and amount of plasticizer led to a different release rate after 2 hours. Best protection was obtained using films plasticized with 20 % of dibutyl phthalate (DBP) allowing a release of only 4 % of the drug in 6 hours although the application temperature was 15 °C below the minimum film-forming temperature (MFT). All coatings dissolved in artificial intestinal fluid within 15 minutes.     

Development of the loratadine gel for enhanced transdermal delivery

Background: The oral administration of loratadine, an antihistamine, can have a variety of adverse side effects, such as headache, fatigue, and nausea, because of the transient high blood concentration. To avoid these effects, loratadine can be administered using a transdermal drug delivery system. Method: This study examined the effects of the drug concentration on drug release from prepared hydroxypropyl methylcellulose gels using a synthetic cellulose membrane at 37°C. The drug concentrations tested were 0.1%, 0.2%, 0.3%, 0.4%, and 0.5% (w/w). The effect of temperature on drug release from the 0.3% loratadine gels was evaluated at 27°C, 32°C, 37°C, and 42°C. Various types of penetration enhancers, such as glycols, glycerides, propylene glycol derivatives, nonionic surfactants, and fatty acids, were incorporated in the gel formulation to increase the level of drug permeation. Results: The rate of drug release increased with increasing drug concentration or temperature. The activation energy for the release of the drug was 5.714 kcal/mol for 0.3% loratadine gel. Among all the enhancers used in this study, polyoxyethylene 2-stearyl ether showed the best enhancing effect. The enhancement factor of the loratadine gel containing the polyoxyethylene 2-stearyl ether was 2.03 compared with that of the loratadine system containing no enhancer. Conclusions: These results suggest that the topical gel formulation of loratadine containing a penetration enhancer could be developed to enhance the penetration of loratadine.     

Influence of Stabilization Temperature on the Entrapment of Adriamycin in Albumin Microspheres

Abstract

Adriamycin associated bovine serum albumin (BSA) microspheres have been prepared by the method involving emulsion and suspension technology. Stabilization of the carrier matrix was achieved by heat treatment at 105, 120, 135 and 150°C.

Following zero to four washings, each of these four batches of microspheres have been evaluated for the amount of associated adriamycin using HPLC. At high stabilization temperatures, migration of adriamycin to the microsphere surface is reduced leading to increased drug entrapment. Results demonstrate that the proportion of entrapped to total drug increases with increase in stabilization temperature of the carrier.     

Development of a taste-masked oral suspension of clindamycin HCl using ion exchange resin Amberlite IRP 69 for use in pediatrics

Purpose: The purpose of this study is to develop an oral suspension of clindamycin resin complex for the potential use in pediatrics.

Methods: Several types of Ion exchange resins were screened for their binding efficiency with clindamycin. In order to develop a suspension formulation, several thickening agents, surfactants, sweeting, and flavoring agents were evaluated for their influence on the release of clindamycin from resinate. Rheological studies were also conducted to select the optimum amounts of the suspending agents. The release profiles of clindamycin in SGF and SIF were also evaluated from freshly prepared suspension and from suspension formulation after storage for 1 month at 25?°C and 40?°C. Clindamycin bitterness threshold was determined based on volunteers’ evaluation, and taste evaluation was conducted in 12 adult volunteers who evaluated the taste of the optimized suspension against clindamycin solution.

Results: Among all resins tested, Amberlite IRP 69 showed the highest binding efficiency to clindamycin. Several excipients were selected into the suspension formulation based on no or minimum influence on the release of clindamycin from the resinate complex. Moreover, xanthan gum was selected as the optimal suspending agent for the suspension. Clindamycin release profiles in SGF or SIF showed 90% release within 30?min from freshly prepared sample. Clindamycin exhibited good stability profiles at 25?°C and 40?°C over 1 month storage. The mean bitterness threshold of clindamycin was 12.5?μg/ml, and taste evaluation study in adults showed sustainable taste improvement for suspension over clindamycin solution.

Conclusion: Clindamycin/resin complexation has shown to be an efficient method to mask the taste of clindamycin and was developed into a suspension formulation that can be used in pediatrics.     

Effect of primary drying temperature on process efficiency and product performance of lyophilized Ertapenam sodium

Abstract

The present work aimed to investigate the impact of primary drying temperature on lyophilization process efficiency and product performance of lyophilized Ertapenam sodium (EPM). Phase behavior of EPM formulation (200?mg/mL) using differential scanning calorimetry (DSC) and freeze drying microscopy (FDM) showed Tg′ at ?28.3?°C (onset) and Tc at ?25.0?°C (onset), respectively. The formulation was freeze dried at different product temperature (Tp) during primary drying, using (a) conservative cycle (CC) where the maximum Tp (?31.9?°C) <Tg′, (b) aggressive cycle 01 (AC01) where the maximum Tp (?24.8?°C) >Tg′, and (c) AC02 where the maximum Tp (?21.0?°C) >Tc. The drying kinetics revealed that the sublimation rate was increased from 0.128?g/h/vial in CC to 0.159 and 0.182?g/h/vial in AC01 and AC02, respectively. This ultimately reduced the primary drying time of 208?min in CC to 145?min in AC01 and to 103?minutes in AC02. Morphological evaluation of cake using scanning electron microscopy (SEM) and texture analysis revealed that AC01 lead to induction of microcollapse, whereas AC02 resulted in collapsed cake. Furthermore, the microcollapsed formulations showed similar physicochemical stability to CC formulation, whereas collapsed cake showed significant degradation of EPM and increased degradation on stress stability. The study highlights that primary drying with microcollapse can be utilized to improve the process efficiency without compromising product quality of amorphous EPM.     

Physicochemical Properties of CWJ-a-5, a New Antitumor 3-Arylisoquinoline Derivative

ABSTRACT

The compound CWJ-a-5 [1-(4-methylpiperazinyl)-3-phenylisoquinoline hydrochloride] is a novel 3-arylisoquinoline derivative which has exhibited potent antitumor activity. As part of an effort to develop a useful formulation for clinical evaluation of this compound, the aqueous stability of CWJ-a-5 as a function of pH, ionic strength, and temperature, as well as its various physicochemical properties, have been examined. The pK_a value obtained by potentiometric titration in methanol–water mixtures was 3.61, at 25°C. The aqueous solubility and the apparent partition coefficient of CWJ-a-5 over the pH range 2.08–9.88 were consistent with those expected of a weak acid of similar pK_a value. The degradation of CWJ-a-5 was found to follow apparent first-order kinetics. The pH–rate profiles generated at 80°C were accounted for by acid-catalyzed degradation at low pH and base-catalyzed degradation at high pH. The activation energy was determined as 22.12 kcal/mol for the degradation of CWJ-a-5 in a pH 2.92 solution with a constant ionic strength of 0.2. Increasing the ionic strength up to 0.9 led to a higher degradation rate constant at pH 2.92. However, CWJ-a-5 was very stable even in a pH 2.92 solution, and its shelf-life was calculated to be 2.03 years at 25°C from the Arrhenius plot.     

Improved oral bioavailability of valsartan using proliposomes: design,characterization and in vivo pharmacokinetics

Abstract

The objective of our investigational work was to develop a proliposomal formulation to improve the oral bioavailability of valsartan. Proliposomes were formulated by thin film hydration technique using different ratios of phospholipids:drug:cholesterol. The prepared proliposomes were evaluated for vesicle size, encapsulation efficiency, morphological properties, in vitro drug release, in vitro permeability and in vivo pharmacokinetics. In vitro drug-release studies were performed in simulated gastric fluid (pH 1.2) and purified water using dialysis bag method. In vitro drug permeation was studied using parallel artificial membrane permeation assay (PAMPA), Caco-2 monolayer and everted rat intestinal perfusion techniques. In vivo pharmacokinetic studies were conducted in male Sprague Dawley (SD) rats. Among the proliposomal formulations, F-V was found to have the highest encapsulation efficiency of 95.6?±?2.9% with a vesicle size of 364.1?±?14.9?nm. The in vitro dissolution studies indicated an improved drug release from proliposomal formulation, F-V in comparison to pure drug suspension in both, purified water and pH 1.2 dissolution media after 12?h. Permeability across PAMPA, Caco-2 cell and everted rat intestinal perfusion studies were higher with F-V formulation as compared to pure drug. Following single oral administration of F-V formulation, a relative bioavailability of 202.36% was achieved as compared to pure valsartan.     

Freeze drying optimization of polymeric nanoparticles for ocular flurbiprofen delivery: effect of protectant agents and critical process parameters on long-term stability

Context: The stabilization of flurbiprofen loaded poly-?-caprolactone nanoparticles (FB-P?CL-NPs) for ocular delivery under accurate freeze-drying (FD) process provides the basis for a large-scale production and its commercial development.

Objective: Optimization of the FD to improve long-term stability of ocular administration’s FB-P?CL-NPs.

Methods: FB-P?CL-NPs were prepared by solvent displacement method with poloxamer 188 (P188) as stabilizer. Freezing and primary drying (PD) were studied and optimized through freeze-thawing test and FD microscopy. Design of experiments was used to accurate secondary drying (SD) conditions and components concentration. Formulations were selected according to desired physicochemical properties. Furthermore, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used to study interactions components.

Results: Optimized FB-P?CL-NPs, stabilized with 3.5% (w/w) P188 and protected with 8% (w/w) poly(ethylene glycol), was submitted to precooling at +10?°C for 1?h, freezing at ?50?°C for 4?h, PD at +5?°C and 0.140 mbar for 24?h and a SD at +45?°C during 10?h. These conditions showed 188.4?±?1.3?nm, 0.087?±?0.014, 85.5?±?1.4%, 0.61?±?0.12%, ?16.4?±?0.1?mV and 325?±?7 mOsm/kg of average size, polydispersity index, entrapment efficiency, residual moisture, surface charge and osmolality, respectively. It performed a long-term stability >12 months. DSC and XRD spectra confirmed adequate chemical interaction between formulation components and showed a semi-crystalline state after FD.

Conclusions: An optimal freeze dried ocular formulation was achieved. Evidently, the successful design of this promising colloidal system resulted from rational cooperation between a good formulation and the right conditions in the FD process.