Formulation Development and Solubility Enhancement of Voriconazole by Solid Dispersion Technique

 

Gaurav Bhaduka^1*, Jitendra Singh Rajawat²

¹Research Scholar, Faculty of Pharmacy, Bhupal Nobles' University,

Maharana Pratap Station Road, Sevashram Circle, Udaipur-313001, Rajasthan, India.

²Assistant Professor, Faculty of Pharmacy, Bhupal Nobles' University,

Maharana Pratap Station Road, Sevashram Circle, Udaipur-313001, Rajasthan, India.

 

ABSTRACT:

The objective of the present investigation was to formulation development of solid dispersion of voriconazole using hot-melt, solvent evaporation and combination of these two methods together with Gelucire^® 44/14, polaxamer 188 and polyvinyl pyrrolidone (PVP) K30 and the different characteristics like drug content analysis and in vitro release of the solid dispersions were investigated. The drug-carriers compatibility of the solid dispersions were investigated by Fourier transform infra-red spectroscopy (FTIR) and differential scanning calorimetry (DSC) study and crystal characteristic of solid dispersions were evaluated by X-ray diffraction (XRD) study. The in vitro release study revealed that among all the physical mixtures and solid dispersions prepared by using different carriers, solid dispersions that contained Gelucire^® 44/14 and Poloxamer 188 as carrier in the ratio of 1:5 (voriconazole: carrier) were released voriconazole in simulated gastric fluid within short period of time. The FTIR spectrum and DSC thermograms indicated the compatibility of drug and carriers. The diffusion exponent (n) determined from in vitro release data of solid dispersions FCG5 and FCP5 were found 0.391 and 0.325, respectively, indicating Fickian drug release mechanism.

 

 

 

1.    INTRODUCTION:

Oral drug delivery is the most convenient and preferred route of drug administration, because of the greater stability, smaller bulk, accurate dosage and easy production. Among the different oral dosage forms, solid dosage form possesses several advantages over other types of oral dosage forms. Last few decades, most of the new chemical entities under development are intended to be used as a solid dosage form which produces an effective reproducible in vivo plasma concentration after oral administration. In fact, most new chemical entities are poorly water-soluble drugs, not well-absorbed after oral administration, which can distract from the drug’s inherent efficacy.

 

The major rate-limiting steps for absorption of drug from the gastrointestinal tract are aqueous solubility and membrane permeability. When delivering an active agent orally, it must first dissolve in gastric and/or intestinal fluids before it can permeate the membranes of the gastro-intestinal tract to reach systemic circulation. Hence, to improve the oral bioavailability of active agents, the pharmaceutical scientists mainly focus on suitable approaches for enhancing solubility and permeability of poorly water-soluble drugs. One of the major current challenges of the pharmaceutical industry is related to develop suitable strategies that improve the water solubility of drug.

 

Solid dispersions are one the most successful and interesting techniques for the improvement of drugs solubility and bioavailability^1,2. Solid dispersion can be defined as a molecular mixture of poorly water-soluble drugs with hydrophilic carriers, either in amorphous, crystalline or molecularly form.

 

 

Voriconazole is a second-generation azole antifungal agent indicated for use in the treatment of fungal infections including invasive apergillosis, esophageal candidiasis and serious fungual infections³. Voriconazole is a lipophilic drug with a low aqueous solubility (maximum 2.7mg/mL), which classifies it to Biopharmaceutical Classification System (BCS) class II^4-7. Its limited solubility in water classified voriconazole as drug with low bioavailability, which limits its effectiveness. This major problem can be solved only by developing suitable pharmaceutical formulations.

 

In the present study, solid dispersions of voriconazole were prepared using hot-melt method, solvent evaporation method and combination of these two methods together with Gelucire^® 44/14, Polaxamer 188 and PVP K30 at drug to carrier ratios of 1:1, 1:3 and 1:5. Drug-excipients interaction was evaluated by FTIR and DSC study and alteration of crystalline form of drug was characterized by XRD technique.

 

2. MATERIALS AND METHODS:

2.1 Materials:

Voriconazole was collected as a gift sample from MSN House, Hyderabad, India. Gelucire^® 44/14 was procured from Coroda, Navi Mumbai, Maharashtra, India. Poloxamer 188 and PVP K30 were procured from Merck, Bangalaru, India.

 

2.2 Methods:

2.2.1 Phase Solubility Study:

Phase solubility study was carried out to investigate the effect of different carriers on the solubility of voriconazole, according to the method reported by Higuchi and Connors⁸. Excess quantity of voriconazole was introduced in 20mL of distilled water containing without or with carrier in different concentration (5%, 10% and 15% w/v). The dispersed media were shaken for 24 hours at room temperature. After 24 h, the dispersed media were filtered through Whatmann^® No. 1 filter paper (0.45µm) and 0.1mL each filtrates were diluted suitably and determined the concentration of voriconazole in diluted filtrate by spectrophotometrically (UV-Visible spectrophotometer, UV-1700, Pharmaspec, Shimadzu, Japan) at 255nm. The phase solubility study of voriconazole in distilled water containing without or with carrier at different concentrations were carried out in triplicate (n = 3) and the mean was considered.

 

2.2.2 Composition of physical mixtures and solid dispersions:

The Gelucire^® 44/14, Poloxamer 188 and PVP K30 were selected as carriers. These three carriers used for the preparation of the solid dispersions and physical mixture and in solvent evaporation method anhydrous methanol were selected as a solvent. The 1:1, 1:3 and 1:5 drug- carrier ratio were selected for melt method, solvent method and combined of these two methods to prepare solid dispersion^9-10.

 

2.2.3 Preparation of physical mixtures:

Physical mixtures (PM) of drug with different carriers were prepared by mixing drug with various carriers at 1:1, 1:3 and 1:5 weight ratios, using glass mortar and pestle, followed by tumbling method in a glass bottle. The mixture was passed through a 60 mesh sieve. The different carriers used for physical mixtures and solid dispersions are presented in Table 1.

 

Table 1: Composition of different physical mixtures and solid dispersions

*Name of the formulations is given as follows-

PMG: Physical mixer prepared with drug and Gelucire^® 44/14 ;

PMP: Physical mixer prepared with drug and Poloxamer 188;

PMK: Physical mixer prepared with drug and PVP K30;

FMG: solid dispersion of drug and Gelucire^® 44/14 were prepared by hot-melt methods;

FMP: solid dispersion of drug and Poloxamer 188 were prepared by hot-melt methods;

FMK: solid dispersion of drug and PVP K30 were prepared by hot-melt methods;

FSG: solid dispersion of drug and Gelucire^® 44/14 were prepared by solvent evaporation methods;

FSP: solid dispersion of drug and Poloxamer 188 were prepared by solvent evaporation methods;

FSK: solid dispersion of drug and PVP K30 were prepared by solvent evaporation methods;

FCG: solid dispersion of drug and Gelucire^® 44/14 were prepared by combination of hot melt and solvent evaporation methods;

FCP: solid dispersion of drug and Poloxamer 188 were prepared by combination of hot melt and solvent evaporation methods;

FCK: solid dispersion of drug and PVP K30 were prepared by combination of hot melt and solvent evaporation methods.

 

2.2.4 Preparation of solid dispersions:

Hot-melt method:

The PM was heated by stirring at 140°C in an oil bath to achieve a homogenous dispersion. When the solid was completely dissolved, the hot liquid was shifted to a water bath with continued stirring. It was then subsequently cooled under the ice cooling. The congealed mass was pulverized, passed through 30 meshes, stored overnight in desiccators and passed through 60 meshes before packing in an airtight container.

 

Solvent evaporation method:

The PM was dissolved in a minimal volume of anhydrous methanol, and the solvent was removed by slow evaporation under reduced pressure. The dried solid dispersions were quench cooling in the freezer (-20°C) for an hour. The dried co-precipitate was passed through 30 meshes, stored in desiccators for two days and passed through 60 meshes before packing in an airtight container.

 

Combination of hot-melt and solvent evaporation methods:

The PM was heated by stirring at 140°C in an oil bath to achieve a homogenous dispersion. When the solid was completely dissolved, the hot liquid was shifted to a water bath with continued stirring. It was then subsequently cooled under the ice cooling. The congealed mass was pulverized, passed through 30 meshes, stored overnight in desiccators and passed through 60 meshes before packing in an airtight container. Next day solid dispersion prepared by hot-melt method was dissolved in a minimal volume of anhydrous methanol and the solvent was removed by slow evaporation under reduced pressure. The dried solid dispersions were quench cooling in the freezer (-20°C) for an hour. The dried co-precipitate was passed through 30 meshes, stored in desiccators for two days and passed through 60 meshes before packing in an airtight container.

 

2.2.5 Drug-carriers compatibility studies:

Compatibility of drug with carriers was investigated by Fourier Transform Infrared spectroscopy (FT-IR) and Differential Scanning Calorimeter (DSC) studies. Powder X-ray diffraction study was performed to evaluate the crystal characteristics drug particles after preparation of solid dispersion.

 

Fourier transform infrared spectroscopy (FTIR):

The FTIR spectra of prepared solid dispersions were recorded using FTIR Spectrophotometer (Prestige-21, Shimadzu, and Tokyo, Japan) by potassium bromide disc technique. The FTIR were scanned in the range of 400 to 4000 cm^-1 at ambient temperature^4-6.

Differential scanning calorimetry (DSC):

DSC thermograms of prepared solid dispersions were investigated using a DSC TA-60 (Shimadzu, Tokyo, Japan). The apparatus was calibrated with purified indium (99.9%). About 1 mg of the sample was sealed in the aluminium pan and heated at the rate of 10°C/min, covering a temperature range of 30°C to 350°C under nitrogen atmosphere, at flow rate of 20ml/min^3-6.

 

2.2.6 Powder X-ray diffraction studies:

X-ray diffractometry of pure drug, physical mixtures and solid dispersions were investigated using Philips XRD Machine set up with generator (PW1830), Goniometry (PW 1820) and diffractometer (PW1710, Eindhoven and Almelo, Netherlands, Europe). The samples were irradiated with Cu K_α radiation at 30 kV voltage and 50mA current with an α₁/α₂ ratio of 0.5. The scanning rate employed was 4^o/min over a diffraction angle of 2θ and range of 5 - 45^{o 4-6}.

 

2.2.7 Characterizations of formulations:

All the physical mixtures and prepared solid dispersions were subjected to evaluate the various characteristics like: drug content analysis and in vitro release studies.

 

2.2.7.1 Drug content analysis:

The drug contents of all solid dispersions were determined by dissolving the sample containing 1.0mg equivalent weight of voriconazole in 50ml methanol. The solution was filtered by using a Whatman filter paper with a pore size 0.45μm. 2ml filtrate was subsequently diluted with 0.1N HCl and volume made up to 10ml. The absorbance was measured using UV-Visible spectrophotometer (pharmaspec-1700, Shimadzu) at 255nm using 0.1N HCl as blank. The drug content analysis of all the formulation were performed six times (n=6)^7-9.

 

2.2.7.2 In vitro release studies:

The in vitro release studies of drug alone, physical mixtures and solid dispersions were carried out by using a USP XXII rotation basket (VEEGO VDA-6D) method at 50rpm. Powder samples of physical mixtures and solid dispersions containing 20mg equivalent weight of voriconazole were filled into a capsule shell. The release medium was consisted of 900ml 0.1(N) HCl and temperature was maintained at 37±0.5°C. At predetermined time intervals, 5ml of samples were withdrawn from the release medium and replaced with fresh release medium to maintain the sink condition. The samples were filtered through Whatmann filter (grade I) paper and the filtrated was suitably diluted. The amount of drug present in the samples was analyzed using UV-Visible spectrophotometer (UV-1800, Shimadzu, Tokyo, Japan) at 255nm. All experiments were carried out in triplicate and the results presented are the mean values of the three experiments; the error bars represent the S.D. Time required to release 90% of voriconazole (t_90%) were calculated_.^6-9.

 

2.2.7.3 Drug release kinetics:

To evaluate the release kinetics of voriconazole from physical mixtures and solid dispersions, the release data were subjected to different kinetic models like: zero-order, first-order and Higuchi ^5,6.

Zero order: Q_t=k₀t………….………………... equation 1

First order: lnQ_t=lnQ₀-k₁t….………………… equation 2

Higuchi’s square root at time: Q_t=K_h t^½..…...... equation 3

 

Where, Q₀ is the initial amount of drug present in the physical mixtures and solid dispersions, Q_t is the percent of drug released at time t and k₀, k₁, and k_h are the zero-order, first-order and Higuchi rate constant, respectively.

 

In order to evaluate the voriconazole release mechanism from physical mixtures and solid dispersion, the release data was further analyzed by Korsmeyer-Peppas equation.

 

M_t/M_∞=kt ⁿ…………………………..………. equation 4

log M_t/M_∞=log k+nlog t………………………equation 5

 

Where, M_t is the amount of drug released at time t and M_∞ is the amount of drug released at infinitive time, M_t/M_∞ is the fraction of drug released at time t. k is the kinetic constant and n is the diffusional exponent. In case of value of diffusional exponent, n <0.45 indicates Fickian or Case I release; 0.45<n<0.89 for non-Fickian or anomalous release; n=0.89 for Case II release; and n>0.89 indicates Super Case II release.

 

2.2.8 Data analysis:

Results are expressed as mean values and standard deviation (±S.D.) and the significance of the difference observed was analyzed by the Student’s t-test. In all tests, a probability value of p < 0.05 was considered statistically significant.

 

3.    RESULTS AND DISCUSSION:

3.1 Phase solubility studies:

The effect of different carriers on the solubility of voriconazole in purified water at room temperature is presented in Table 2. The saturation solubility of voriconazole was enhanced in all cases, as compared to the control, pure voriconazole. It was also observed that increased in carrier in weight fraction resulted in an increased in drug solubility.

 

3.1 Preparation of solid dispersions:

Solid dispersions of voriconazole were prepared by various techniques and to prepare voriconazole formulations three carriers were selected, out of which two carriers are basically surface-active agents and another carrier is a polymeric materials.

 

3.2 Drug-excipients compatibility studies:

3.2.1 FT-IR Analysis:

The FTIR spectra of voriconazole, Gelucire^® 44/14, physical mixtures [PMG5] and solid dispersions of voriconazole with 1:5 ratio of Gelucire^® 44/14 prepared by combined method of hot melt and solvent evaporation [FCG5] are shown in Fig. 1. The FTIR spectra of Poloxamer 188, physical mixtures [PMP5] and solid dispersions of voriconazole with 1:5 ratio of Poloxamer 188 prepared by combined method of hot melt and solvent evaporation [FCP5] are shown in Fig. 2. The FTIR spectra of PVP K-30, physical mixtures [PMK5] and solid dispersions of voriconazole with 1:5 ratio of PVP K-30 prepared by solvent evaporation method [FSK5] are shown in Fig. 3. The FTIR spectrum of voriconazole showed sharp peaks at 3327 cm^-1 (N-H stretching), 3227 cm^-1 (O-H stretching), 1718 cm-1 (C-O stretching), 1587.44–1451.28 cm⁻¹ (C-F stretching), 1510.28–1451.28 cm⁻¹ (C-N stretching) and 1044 cm-1 (S=O stretching). The FTIR spectrum of Gelucire® 44/14 showed characteristic peaks at 2919.98 and 2855.94 cm^-1 (C-H stretching), 1730.35 cm^-1 (C=O stretching) and 1117.46 cm^-1 (C-O stretching). The FTIR spectrum of Poloxamer 188 showed sharp bands at 3444.70 cm^-1 (O-H stretching), 2886.54 cm^-1 (C-H stretching) and 1968.34 and 1667.81 cm^-1 (C=O stretching). The FTIR spectrum of PVP K-30 exhibited sharp peaks at 3401.67 cm^-1 (O-H stretching), 2954.21 cm^-1 (C-H stretching), 1664.91 cm^-1 (C=O stretching) and 1354.71 cm^-1 (C-O stretching). The FTIR spectra of physical mixtures and solid dispersions were equivalent to the addition of spectrum of drug and carriers. In the physical mixtures and solid dispersions the peaks due to O-H stretching and N-H stretching were also exhibited. These results indicated absence of well-defined interaction between drug and carriers.

 

Table 2: Effects of different carriers on the solubility of voriconazole (mg mL^-1) in purified water at room temperature (Mean ± S.D.; n = 3)

 

Fig. 1: FTIR spectra of voriconazole, Gelucire^® 44/14, physical mixtures [PMG5] and solid dispersions of voriconazole with 1:5 ratio of Gelucire^® 44/14 prepared by combined method of hot melt and solvent evaporation [FCG5].

 

 

Fig. 2: FTIR spectra of voriconazole, PVP K-30, physical mixtures [PMP5] and solid dispersions of voriconazole with 1:5 ratio of Poloxamer 188 prepared by combined method of hot melt and solvent evaporation [FCP5].

 

 

Fig. 3: FTIR spectra of voriconazole, PVP K-30, physical mixtures [PMK5] and solid dispersions of voriconazole with 1:5 ratio of PVP K-30 prepared by combined method of hot melt and solvent evaporation [FSK5].

 

3.2.2 DSC:

The thermogram of voriconazole showed a single sharp endothermic peak at 132.47^∘C corresponding to the melting of voriconazole. The DSC curve for each carrier have a single endothermic peak for the melting point of Gelucire® 44/14 (48.2^oC), Poloxamer 188 (54.2^oC) and PVP K-30 (65.03^oC). The thermogram of all physical mixtures (PMG5, PMP5 and PMK5) containing different carriers showed two peaks corresponding to voriconazole and individual carrier. However, a considerable decreased in peak height of the thermograms were observed in physical mixture. This suggested that the presence of significant portion of voriconzaole and individual carrier in the physical mixtures in amorphous form. The thermograms of solid dispersions prepared by using different carriers showed only one peak. The thermograms of solid dispersions prepared by using Gelucire® 44/14 (FCG5) and PVP K-30 (FSK5) showed only peak at 131.56^oC and 131.30^oC, respectively. The position of endothermic peak of FCG5 and FSK5 corresponding to temperature showed in similar position as that of position of endothermic peak (132.41^oC) of pure voriconazole. However, the absence of Gelucire® 44/14 and PVP K-30 peak in the solid dispersions demonstrated that both the carriers could be dispersed homogenously in the amorphous state in the solid dispersions. The thermogram of solid dispersion (FCP5) prepared by using 188 showed a single peak at 116.66^oC, indicated the shifting of peak position. The reduction in endothermic peaks and significant shift in the endothermic peaks might be due to partial conversation of crystalline form of voriconazole to amorphous form. The thermograms showed no evidence of the formation of solid complex or any chemical interaction between drug and carrier.

 

3.3 XRD Study:

X-ray diffraction studies were performed to evaluate any change in the crystallinity of the drug when formulated into physical mixtures or solid dispersion. Voriconzaole is a crystalline drug and it exhibited characteristic peaks at 12.6, 13.8, 16.5, 17.4, 19.7, 21.2, 24.4, 26.0 and 35.1 corresponding to 2θ value. The diffractogram of different carriers were also studied for Gelucire^® 44/14, Poloxamer 188 and PVP K-30. The distinguished peaks were observed in the carriers of Gelucire^® 44/14 (17.8, 21.4, 27.1 and 34.1) and Poloxamer 188 (19.3, 23.2 and 26.4) showed distinguished peaks. However, in the diffractogram of PVP K-30, any kind of peaks were not observed. This might be due to amorphous nature of PVP K-30. The X-ray diffraction pattern of physical mixtures prepared by using Gelucire^® 44/14 (PMG5), Poloxamer 188 (PMP5) and PVP K-30 (PMPK5) exhibited diffraction peaks of high, medium and low intensities. In all solid dispersions the diffraction peaks were not observed. The diffractorgram of solid dispersions depicted the presence of voriconazole in the amorphous state.

 

3.4 Drug content analysis:

The drug content of different physical mixtures and solid dispersions were studied. The drug content all the physical mixtures and solid dispersion were found within the range of 96.59±1.26 to 99.24±0.42. Good uniformity in drug content was observed in all physical mixtures and solid dispersions.

 

3.5 In vitro release studies:

The in vitro release data of the different physical mixtures and solid dispersions were studied. Physical mixture (PMG5) containing Gelucire^® 44/14 as carrier in the drug:carrier ratio 1:5 exhibited maximum (70%) release within 2 hrs. Solid dispersion contained Gelucire® 44/14 prepared by combined hot melt and solvent evaporation methods demonstrated almost 100% voriconazole was released within 2 hrs. However, solid dispersion (FCG5) prepared by combined hot melt and solvent evaporation methods contained drug and Gelucire^® 44/14 in the ratio of 1:5 was released 100% of voriconazole within 75 minutes. Solid dispersions prepared by combined hot melt and solvent evaporation methods contained drug and Polaxamer 188 in the ratio of 1:3 (FCP3) and 1:5 (FCP5) showed release of almost all the drug from the solid dispersions within 1.5hrs. Solid dispersion (FCP5) was released 100% of voriconazole within 90 minutes (Table 3). However, solid dispersion prepared by different ratios (1:1, 1:3 and 1:5) of drug and PVP K30 showed not more than 85% release within 2 hrs. The in vitro release profile of different physical mixtures and solid dispersions are depicted in Fig. 4, Fig. 5, Fig. 6 and Fig. 7. The release profiles portrait that the release of voriconazole was increased from physical mixtures and solid dispersions. The increased of release of voriconzaole from physical mixtures might be due to formation of coat of hydrophilic carriers and render them more hydrophilic. In case of solid dispersion, the release of voriconazole was increased due to decreased of crystallinity and presence of voriconazole in amorphous form within the solid dispersions. Release parameter like: time to released 90% (t_90%) of voriconazole from physical mixtures and solid dispersions prepared by different carriers are presented in Table 4.

 

Table 3: % cumulative amount of voriconazole released from various solid dispersion formulations prepared with Gelucire^® 44/14* and Poloxamer 188*.

*In vitro release of all formulations was carried out three times. Here, the mean value was considered.

 

Table 4: Time to release 90% of voriconazole (t_90%) from physical mixtures and solid dispersion prepared using various polymers and its pure form.

 

 

 

Table 5: Release kinetics and release mechanism of voriconazole from solid dispersions of FCG5 and FCP5.

Formulation Code	Release kinetics and release mechanism
	Zero Order		First Order		Higuchi		Korsmeyer Peppas
	(R2)	K0	(R2)	K1	(R2)	Kh	(R2)	n	K
FCG5	0.847	1.226	0.925	-0.031	0.982	11.80	0.959	0.391	1.275
FCP5	0.775	0.970	0.953	-0.029	0.958	10.73	0.956	0.325	1.380

 

Fig. 4: In-vitro drug release profiles of pure drug, physical mixtures (PMG1, PMG3, PMG5, PMG1, PMG3, PMG5, PMK1, PMK3 and PMK5). Mean percentage release was considered for construction of release profile (n = 3).

 

Fig. 5: In-vitro drug release profiles of pure drug, physical mixtures (PMG1, PMG3 and PMG5) and various formulations prepared by Gelucire^® 44/14 (FMG1, FMG3, FMG5, FSG1, FSG3, FSG5, FCG1, FCG3 and FCG5). Mean percentage release was considered for construction of release profile (n = 3).

 

Fig. 6: In-vitro drug release profiles of pure drug, physical mixtures (PMP1, PMP3 and PMP5) and various formulations prepared by Poloxamer 188 (FMP1, FMP3, FMP5, FSP1, FSP3, FSP5, FCP1, FCP3 and FCP5). Mean percentage release was considered for construction of release profile (n = 3).

 

Fig. 7: In-vitro drug release profiles of pure drug, physical mixtures (PMK1, PMK3 and PMK5) and various formulations prepared by PVP K30 (FSK1, FSK3 and FSK5). Mean percentage release was considered for construction of release profile (n=3)

 

3.6 Drug release kinetic studies:

The release kinetic studies of in vitro released data and release mechanism of voriconazole from physical mixtures and solid dispersions were evaluated. The release kinetic study of physical mixtures and solid dispersions prepared by using different carriers followed first order kinetic except solid dispersions FMG1, FMG3 and FCG1. This indicates the release of voriconazole from the physical mixtures and solid dispersions dependent on the concentration of voriconazole in the formulations. The release kinetic followed Higuchi kinetic indicated the release of voriconazole followed diffusion controlled through carriers. The high R² value of Korsmeyer-Peppas model clearly indicated the release mechanism of voriconazole from physical mixtures and solid dispersions were strongly dependent on model. The diffusion exponent (n) determined from in vitro release data of solid dispersions FCG5 and FCP5 were found 0.391 and 0.325, respectively, indicating Fickian drug release mechanism (Table 5).

 

CONCLUSIONS:

The present work involves the development of suitable formulation to enhance the dissolution rate of voriconazole in gastric fluid and to improve the oral bioavailability. In the present study, among all the physical mixtures and solid dispersions prepared by using different carriers using different methods like: hot-melt method, solvent-evaporation method and combination of above both the method, solid dispersions that contained Gelucire^® 44/14 (FCG5) and Poloxamer 188 (FCP5) as carrier in the ratio of 1:5 (voriconazole: carrier) were released voriconazole in simulated gastric fluid within short period of time.

 

CONFLICT OF INTEREST:

Authors are hereby declared that there is no conflict of interest for publication of this manuscript.

 

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Received on 13.01.2020          Modified on 28.02.2020

Accepted on 11.04.2020         © RJPT All right reserved