Understanding the relationship between wettability and dissolution of solid dispersion

Accepted Manuscript Title: Understanding the Relationship between Wettability and Dissolution of Solid Dispersion Author: Yi Lu Ning Tang Ruyue Lian Jianqing Qi Wei Wu PII: DOI: Reference:

S0378-5173(14)00086-6 http://dx.doi.org/doi:10.1016/j.ijpharm.2014.02.004 IJP 13879

To appear in:

International Journal of Pharmaceutics

Received date: Revised date: Accepted date:

17-10-2013 17-12-2013 2-2-2014

Please cite this article as: Yi LuNing TangRuyue LianJianqing QiWei Wu Understanding the Relationship between Wettability and Dissolution of Solid Dispersion (2014), http://dx.doi.org/10.1016/j.ijpharm.2014.02.004 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Understanding the Relationship between Wettability and Dissolution of Solid

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Dispersion

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Yi Lu, Ning Tang, Ruyue Lian, Jianqing Qi, Wei Wu*

School of Pharmacy, Fudan University, Shanghai 201203, PR China

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E-mail address: [email protected]

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Corresponding author. Tel.: +86 28 51980084; fax: +86 21 51980084.

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ABSTRACT Improved wettability has been ascribed to one of the important mechanisms for

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enhanced dissolution of solid dispersions. But its relationship with dissolution has not

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been closely studied to date. In this study, solid dispersion of simvastatin (SV) and

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polyvinylpyrrolidone (PVP) was prepared without and with sodium dodecyl sulfate

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(SDS) incorporated, respectively. The dissolution, contact angle and water absorption

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rate of these solid dispersions were measured to elucidate the relationship between

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wettability and dissolution. An abrupt increase of dissolution was observed when PVP

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amount exceeded a critical value. Contact angle was decreased with increasing of

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PVP amount. And the dissolution efficiency of the solid dispersion was increased with

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the decreasing of the contact angle, which was divided by a critical angle of 40.8° into

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two linear parts. The result was validated in the dissolution of SDS incorporated solid

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dispersions. Contact angle correlated well with water absorption rate. A critical water

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absorption rate, with value of 0.535 μL/min, was also observed for the transition of

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dissolution efficiency. In conclusion, both contact angle and water absorption rate are

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good indicators for dissolution transition of solid dispersion, which show great

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potential in formula screening of solid dispersion.

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Keywords: wettability, dissolution, contact angle, water absorption, solid dispersion,

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simvastatin

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1. Introduction Dispersion of poorly water-soluble drug into solid inert hydrophilic polymer

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matrices, so called as solid dispersion, has been well established as an efficient

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approach to enhance the dissolution and hence the oral bioavailability of these drugs

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(Bikiaris, 2011; Kim et al., 2011). The rationale for enhanced dissolution is the high

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dispersity of drug molecules that results in increased dissolution surface as understood

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from the Noyes-Whitney equation (Alam et al., 2012; Srinarong et al., 2011). Equally

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important is that the hydrophilic polymers help to improve the wettability of the

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poorly water-insoluble drugs, which is crucial for the dissolution (Frizon et al., 2013;

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Gorajana et al., 2013).

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However, only a limited number of products can be available on market despite the

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intense studies on solid dispersions. Poor predictability of solid dispersion behavior

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was ascribed to one of the main reasons (Dahlberg et al., 2008). Although the

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dispersity of drug molecules was usually used to identify the formation of solid

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dispersion, its role in interpreting the dissolution profiles of solid dispersions is very

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limited. For instance, in our previous studies with silymarin/polyvinylpyrrolidone

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(PVP) and lansoprazole/PVP solid dispersion (Sun et al., 2008; Zhang et al., 2008),

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there was an abrupt increase in dissolution rate when the PVP amount exceeded a

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critical point. However, amorphous drug dispersion had already formed before

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reaching this critical point as characterized by DSC and X-ray diffraction. There

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seems to be some other mechanisms that govern the dissolution rate of drugs from

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solid dispersions. Deciphering the critical properties that directly connected to the

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dissolution transition will provide a nice tool to predict the dissolution behavior of

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solid dispersions. Wetting is the first step for a solid oral drug delivery system to dissolve (Dahlberg

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et al., 2008). The wettability of solid dispersions also correlate to improved intrinsic

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dissolution for poorly water soluble drugs (Chokshi et al., 2007). However, the

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wettability of solid dispersions is determined by their surface chemical composition. It

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is reported that the surface of a spray-dried powder is dominated by less soluble

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material due to its adsorption to air/liquid interface before it turns into a dry particle

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(Dahlberg et al., 2008; Elversson and Millqvist-Fureby, 2006; Millqvist-Fureby and

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Smith, 2007). Therefore, although the drug has got maximum dispersity, it is possible

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that the wettability of the solid dispersion do not get significantly improved due to the

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accumulation of the dispersed drug in surface. But the further increased hydrophilic

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carrier might change the surface composition of the resulted solid dispersion and

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increase its wettability. Previous data implied that there was direct correlation

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between the wettability and dissolution rate of solid dispersions. However, little work

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has been done to illustrate whether there was critical wettability parameters that

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correlated to the dissolution transition behavior.

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In this study, the wettability of solid dispersions with different drug/carrier ratios

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was measured and correlated to the dissolution profiles. Simvastatin (SV)/PVP solid

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dispersion were prepared by a fluid-bed coating technique with SV/PVP weight ratios

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varying from 1/2.0 to 1/4.0. Solid dispersion incorporated with various sodium

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dodecyl sulfate (SDS) content were also prepared in a fixed SV/PVP ratio of 1/3. The 4

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dissolution, contact angle and water absorption rate of all these solid dispersions were

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measured to evaluate the relationship between dissolution and wettability.

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2. Materials and methods

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2.1. Materials

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Simvastatin was purchased from Apeloa Kangyu pharmaceuticals (Zhejiang,

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China)

a

purity

of

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98%.

Polyvinylpyrrolidone

(PVP,

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PlasdoneK29/32®) was kindly gifted from ISP China (Shanghai, China). Non-pareil

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pellets (sugar spheres, 710-850 μm) were provided by by Gaocheng Biotech and

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Health Co, Ltd (Hangzhou, China). Chromatographic methanol was a TEDIA product

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(USA). Deionized water was prepared by a Milli-Q water purifying system

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(Millipore, USA). All other reagents were of analytical grade.

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2.2. Preparation of solid dispersions

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SV solid dispersion pellets were prepared in a fluid-bed coater (DPL1/3

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Multiprocessor, Chongqing Jinggong Pharmaceutical Machinery Co., Ltd, China)

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(Sun et al., 2008; Zhang et al., 2008; Zhang et al., 2009). Firstly, SV and the carriers

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were dissolved in ethanol under continuous stirring till a homogeneous solution was

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obtained. The concentration of total mass of drug and carrier was adjusted to 10%.

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The final solution was then sprayed through a nozzle onto fluidized sugar spheres.

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The detailed operating conditions were as follows: inlet air temperature, 40-50°C;

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product temperature, 28°C; blower frequency, 15 Hz; rotational speed of peristaltic 5

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pump, 12 rpm; atomizing air pressure, 0.2 mPa; spray nozzle diameter, 0.5 mm. After

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completion of solid dispersion layering, the pellets were dried for further 15 min at 30

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°C. The SV/PVP solid dispersion were prepared at incremental weight ratios of

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SV/PVP in an interval of 0.1 from 1/2.0 to 1/4.0. Solid dispersions were also prepared

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in a fixed SV/PVP ratio of 1/3 incorporated with 0.5%, 1.0% and 1.5% SDS of total

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mass of SV and PVP.

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In order to prepare cylindrical tablet for measurement of contact angle, the solid

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dispersion powders were also prepared by spraying into the drying chamber without

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sucrose spheres under the same coating conditions and collected at the bottom.

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2.3 Determination of SV by HPLC

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SV in solid dispersion and dissolution medium was determined by HPLC. The

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Agilent 1100 series HPLC system (Agilent, USA) consisted of a quaternary pump, a

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degasser, an autosampler, a column heater, and a tunable ultraviolet detector. SV was

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separated by a C18 column (Diamonsil, 5μm, 4.6 mm×250 mm, Dikema, China)

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guarded with a refillable precolumn (C18, 1.0 mm×20 mm, Alltech, USA) at 40 °C

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and detected at 238 nm. The mobile phase consisting of 90% methanol aqueous

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solution (adjusted by 0.1% phosphoric acid solution to pH 4.0) was pumped at a flow

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rate of 1.0 mL/min.

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2.4 Dissolution studies

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The dissolution studies were conducted using a ZRS-8G dissolution tester (Tianjin,

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China) based on the Chinese Pharmacopoeia Method I (rotating basket method). 6

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Samples containing 20 mg of SV were sealed in hard gelatin capsules, then put into

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the rotating basket and immersed in 900 mL of dissolution medium thermostatically

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maintained at 37±0.5 °C at a rotation rate of 100 rpm. At appropriate time intervals, 5

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mL of the sample was withdrawn and filtered (Millex® AP, Millipore, 0.4 μm). The

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filtrate was analyzed by HPLC for SV as described above. At the meantime, an equal

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volume of the same blank medium was added to keep constant volume. The

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dissolution data were obtained in triplicate.

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Dissolution efficiency (DE) is defined as percentage of the area under the

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dissolution curve up to a certain time (t), occupying in the area of the rectangle

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described by 100% dissolution in the same time (Costa and Sousa Lobo, 2001). It can

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be calculated by the following equation:

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where y is the drug dissolved percentage at time t, y100 means 100%.

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2.5 Determination of the contact angle

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Contact angle was measured using an image analysis method (Karavas et al., 2006;

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Tian et al., 2007). Cylindrical tablets of tested material with a diameter of 12 mm and

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a weight of 300 mg were prepared using Rimek mini PRESS-II SF (Karnavati

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Engineering, India). The compression force was 1000 kg for 5 s. Then 20ul purified

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water was dropped onto the upper surface of the tablets, which were immediately

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photographed by a Teli CCD camera of OCA 15 Plus apparatus (DataPhysics

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Instruments GmbH, Germany). The digital drop image was processed by an image

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analysis system after magnification of the photographs to get the contact angle. 7

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2.6 Measurement of the water absorption rate The ‘Enslin-Neff’ apparatus, shown in Fig.1, was employed to measure the water

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absorption rate (Enslin, 1933; Jacques and Buri, 1997; Kuno et al., 2008; Nogami et

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al., 1969) . A given amount of powder (15 mg) was packed in a glass tube with a filter

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paper at the bottom by tapping mechanically to get an equilibrium depth of bed. Then

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the tube was closely connected to the glass filter plate through the filter paper and

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timed when water absorption initiated. The volume of water (v) happened to wet the

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whole powder bed and the corresponding time (t) was recorded. The water absorption

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rate was calculated with the division of v by t.

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Insert Fig.1 here

3. Results and discussion

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3.1 Dissolution of SV/PVP solid dispersion

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Dissolution of SV/PVP solid dispersions with different ratios of SV/PVP in 0.2%

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SDS solution was shown in Fig. 2. Wetting is prerequisite for SV to dissolve due to its

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strong hydrophobicity. Thus SV exhibited a sigmoid dissolution curve with a time lag

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of about 10 min. An elevated dissolution amount after 45 min was also observed for

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SV, which is comparable with that of solid dispersions with SV/PVP ratio of 1/3.7 and

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1/3.8 (Fig. 2. B).

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The dissolution rate of the solid dispersion increased with the increasing of

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SV/PVP ratio (Fig. 2.). The dissolution curves could be divided into four zones by

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SV/PVP ratio of 1/2.9, 1/3.6 and 1/3.8 as judged from the similarity factor f2 (Table 8

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1.). As far as the region with drug/carrier ratio lower than 1/2.9 was concerned, the

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initial dissolution rate of solid dispersions within 5 min was higher than SV, which

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complied with the concept of enhanced dissolution commonly accepted for solid

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dispersion and would be ascribed to the inhibition of SV crystalline by PVP. However,

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the ultimate dissolution of these solid dispersions was inferior to SV powder. The

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possible reason for this is that the amount of PVP was not sufficient to inhibit the

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crystallization of SV in the process of solvent evaporation. On the contrary, the

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viscous dissolution front induced by PVP could inhibit the dissolution of SV (Doherty

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and York, 1987). Moreover, an abrupt increase in dissolution was observed between

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the SV/PVP ratios from 1/3.0-1/3.6 segment to 1/3.9 with an increasing of dissolution

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percent from about 60% to 100%, implying a solid dispersion status change from

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“drug-controlled” to “polymer-controlled” (Doherty and York, 1987; Karavas et al.,

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2006; Kim et al., 2006).

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Insert Fig. 2 about here

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It has been shown that the surface of a spray-dried powder is dominated by less

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soluble material (Dahlberg et al., 2008; Elversson and Millqvist-Fureby, 2006;

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Millqvist-Fureby and Smith, 2007). With regard to SV/PVP solid dispersion, SV has

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stronger affinity for liquid/air interface than PVP and thus with more tendency to

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dominate the surface of the dried layer. At lower amount of PVP, such as less than 3.6

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times of SV, SV molecules might migrate towards the powder surface and a “drug-

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controlled” solid dispersion status might be formed. The hydrophobic nature of SV

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would render the powder surface with a low wettability and hinder the penetration of 9

Page 9 of 22

solution. Thus the solid dispersion with PVP amount less than 3.6 times of SV got a

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final dissolution percent less than 70%. With the increase of PVP amount, such as

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more than 3.9 times that of SV, excess PVP might cover the powder surface and a

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“polymer-controlled” solid dispersion status was formed. And the solid dispersion

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powder might have high wettability due to the hydrophilic nature of PVP. Therefore,

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solid dispersion with PVP amount exceeding 3.8 times of SV exhibited superior

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dissolution. Between these two solid dispersion status, a transitional status might exist

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as outlined by Higuchi et al. (Higuchi, 1967; Higuchi et al., 1965). Solid dispersions

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with SV/PVP ratio of 1/3.7 and 1/3.8 might stand at the transitional status, which

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probably exhibited a critical wettability.

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In order to validate the solid dispersion behavior transition with SV/PVP ratio,

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dissolution in poor solvents, such as pure water and phosphate buffered solution

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(PBS, pH 6.8), were performed to exclude the solubilization effect of SDS. But the

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SV/PVP ratio was fixed between 1/3.0 and 1/4.0. Since sink condition was not

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achieved in these two medium, SV powder dissolved about 2% of total amount while

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solid dispersion got maximum dissolution around 40% (Fig. 3 A and B). The overall

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trend in dissolution enhancement was similar to that in 0.2% SDS solution, i.e.

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dissolution was increased with increasing of PVP amount. There were also different

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dissolution regions divided by SV/PVP ratio. A dissolution leap could also be

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observed around SV/PVP ratio of 1/3.6. The wettability alteration due to surface

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composition transition in different solid dispersion status is still the reason for

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dissolution leap. But the critical SV/PVP ratio dividing dissolution regions was

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different in different dissolution medium, which might be ascribed to wettability

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variation induced by composition of dissolution medium (Krawczyk et al., 2013).

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3.2 Contact angle

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Insert Fig. 3 about here

The wettability is usually indicated by contact angle. The limits of contact angle are

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0° for complete wetting and 180° for no wetting. Although contact angle can be

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altered in different solution, water was regularly adopted to be the wetting solution in

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the test (Karavas et al., 2006; Tian et al., 2007). The contact angle of this article was

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unified to be measured in pure water in order to get a better comparison. The contact

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angle of SV and solid dispersion was shown in Table 2. Being a poorly water-soluble

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drug, SV got a contact angle of 67.0 ± 1.13°, while 27.5 ± 2.62° for PVP as being

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water-soluble. Introduction of PVP did decrease the contact angle of SV, meaning

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increasing of wettability. The contact angle got continuous decrease with increasing

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of PVP amount. However, the contact angle reached a transition point when PVP

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amount increased to 3.6 times of SV, and continued to decrease to 37.5±1.63° at

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SV/PVP ratio of 1/4.0. The solid dispersion with SV/PVP ratio around 1/3.6 actually

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lies in the transitional phase as indicated in dissolution in 0.2% SDS. In view of this,

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wettability as indicated by contact angle dose reflect the transition of solid dispersion

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status.

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Insert Table 2 about here

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In order to find the critical contact angle, the DEs of solid dispersion in 0.2% SDS

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was plotted versus their contact angles (Fig. 4 A). A general trend is observed for 11

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increasing of DE with decreasing of contact angle, which was presented as two linear

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intersection parts. The intersection point is the critical contact angle, which was

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calculated to be 40.8°. The calculated value coincides well with the transition point of

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the contact angle along with the variation of SV/PVP ratio, which was observed to be

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around 40° (Table 2). Moreover, the DEs in PBS and water were respectively plotted

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versus corresponding contact angle values (Fig. 4 B). It was shown that DE got

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significantly increase when the contact angle was reduced under the critical value

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regardless of the dissolution medium.

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Insert Fig. 4 about here

3.3 Effects of incorporated SDS on dissolution

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Dissolution of SV/PVP solid dispersion in fixed drug/carrier ratio of 1/3 without

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and with 0.5%, 1.0% and 1.5% SDS incorporated were shown in Fig. 5. Dissolution

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was increased with the increase of incorporated SDS in all tested dissolution medium.

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But the effects of SDS on dissolution improvement seemed more significant in water

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and PBS than in 0.2% SDS solution. With small amount of 0.5% SDS incorporated,

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the dissolution amount during 45 min could be increased from 2.50% to 15.01% in

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pure water, and from 0.47% to 13.67% in PBS. However, the contact angle value for

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0.5% SDS incorporated solid dispersion was comparative to that of solid dispersion

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without SDS incorporated (Table 2). These two solid dispersions therefore should

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exhibit similar dissolution. The SDS incorporated solid dispersion will produce a SDS

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rich diffusion layer (Craig, 2002). Since drug was released from the diffusion layer

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into the medium, SDS incorporated solid dispersion will get a higher concentration of

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SV in the dissolution front and hence a better dissolution. This supposition was

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exemplified by the dissolution results in 0.2% SDS solution. When 0.2% SDS was

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used as dissolution medium instead of water and PBS, the SDS dissolved from solid

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dispersion into the diffusion layer will be negligible. Therefore, the dissolution

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behavior of solid dispersion without SDS became similar to that with 0.5% SDS

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incorporated. Nevertheless, as judged by f2 value, the dissolution of these two solid

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dispersions was coincident in both water (f2=50.24) and PBS (f2=55.07). With

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increase of incorporated SDS to 1.0% and 1.5%, the contact angle of the solid

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dispersions was further decreased (Table 2) and thus the dissolution was further

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increased (Fig. 5). And the contact angle of the solid dispersions was lower than the

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critical value of 40.8° when incorporated SDS amount increased beyond 1.0%.

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Therefore the dissolution efficiency exhibited an abrupt increase (Fig. 4 C), which is

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similar to the results of SV/PVP solid dispersion.

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Actually, the dissolved SDS from solid dispersion could only reach a concentration

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of 0.0001% at most, far less than its critical micelle concentration. Then the

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solubilization effects from incorporated SDS contribute very limited to dissolution,

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which is especially true in the case of dissolution in 0.2% SDS solution. However, as

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a hydrophilic surfactant, incorporation of SDS, even with small amount, decreased the

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contact angle significantly (Table 2). The results again confirmed the importance of

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wetting to dissolution of solid dispersions. Furthermore, it is the improved wettability

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that promoted the emerging of third generation of solid dispersions, which contain a

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surfactant carrier, or a mixture of amorphous polymers and surfactants as carriers 13

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(Vasconcelos et al., 2007). However, the critical contact angle designates the direction

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of formula screening.

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3.4 Water absorption rate

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Insert Fig. 5 about here

Measurement of contact angle might be difficult since pre-processing such as

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tableting and specified instrument are required. Wettability can be regarded as the

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ability of a bulk powder to imbibe a liquid (Dahlberg et al., 2008), then the water

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absorption rate might be an alteration to contact angle. The water absorption rates of

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solid dispersion powders were shown in Table 2. A linear relationship was observed

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between contact angles and the water absorption rates with a correlation coefficient of

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0.9855 (r2 = 0.9712) as shown in Fig. 6. The value is far greater than the critical value

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of the correlation coefficient (α=0.05), which indicates that water absorption rate

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strongly correlated to contact angle and could be used to indicate the wettability of

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powder. The DE was increased with the increase of water absorption rate (Fig. 7). The

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trend was also divided into two linear increasing parts by an intersection point, which

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could be regarded as the critical water absorption rate with a calculated value of 0.535

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μL/min. Similarly, at water absorption rate exceeding the critical value, the DE will

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get significantly increase regardless of the dissolution medium (Fig. 7).

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Insert Fig. 6 about here

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Insert Fig. 7 about here

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4. Conclusion Wettability is indeed one of the most important factors dominating dissolution of

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solid dispersions. Critical contact angle is a good indicator for dissolution transition,

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which can be potentially used to screen formulation of solid dispersions. Water

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absorption rate correlates well with contact angle. Critical water absorption rate can

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substitute critical contact angle in the indication of dissolution transition.

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Acknowledgement

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This work was financially supported by Shanghai Municipal Commission

Science

and

Technology

(11DZ1920200

and

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11DZ1920906). Dr. Wu would like to thank the Shanghai Commission of

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Education (10SG05) and Ministry of Education (NCET-11-0114) for

306

personnel fostering funding.

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Kim, E.J., Chun, M.K., Jang, J.S., Lee, I.H., Lee, K.R., Choi, H.K., 2006. Preparation

350

of a solid dispersion of felodipine using a solvent wetting method. Eur. J. Pharm.

352 353

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d

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Biopharm. 64, 200-205.

Kim, K.T., Lee, J.Y., Lee, M.Y., Song, C.K., Choi, J., Kim, D.-D., 2011. Solid Dispersions as a Drug Delivery System. J. Pharm. Invest. 41, 125-142.

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Krawczyk, J., Szymczyk, K., Zdziennicka, A., Janczuk, B., 2013. Wettability of

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polymers by aqueous solution of binary surfactants mixture with regard to

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adhesion in polymer-solution system II. Critical surface tension of polymers

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wetting and work of adhesion. Int. J. Adhes. Adhes. 45, 106-111.

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Kuno, Y., Kojima, M., Nakagami, H., Yonemochi, E., Terada, K., 2008. Effect of the

359

type of lubricant on the characteristics of orally disintegrating tablets 17

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manufactured using the phase transition of sugar alcohol. Eur. J. Pharm.

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363

Millqvist-Fureby, A., Smith, P., 2007. In-situ lecithination of dairy powders in spraydrying for confectionery applications. Food Hydrocolloid. 21, 920-927.

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Nogami, H., Nagai, T., Fukuoka, E., Sonobe, T., 1969. Disintegration of the aspirin

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tablets containing potato starch and microcrystalline cellulose in various

366

concentrations. Chem. Pharm. Bull. 17, 1450-1455.

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cr

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Srinarong, P., de Waard, H., Frijlink, H.W., Hinrichs, W.L.J., 2011. Improved

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dissolution behavior of lipophilic drugs by solid dispersions: the production

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process as starting point for formulation considerations. Expert Opin. Drug

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an

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Sun, N., Wei, X., Wu, B., Chen, J., Lu, Y., Wu, W., 2008. Enhanced dissolution of

372

silymarin/polyvinylpyrrolidone solid dispersion pellets prepared by a one-step

Ac ce pt e

373

d

371

fluid-bed coating technique. Powder Technol. 182, 72-80.

374

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375

C.J., Rantanen, J., Rades, T., 2007. Influence of polymorphic form, morphology,

376 377

and excipient interactions on the dissolution of carbamazepine compacts. J. Pharm. Sci. 96, 584-594.

378

Vasconcelos, T., Sarmento, B., Costa, P., 2007. Solid dispersions as strategy to

379

improve oral bioavailability of poor water soluble drugs. Drug Discov. Today 12,

380

1068-1075.

381

Zhang, X., Sun, N., Wu, B., Lu, Y., Guan, T., Wu, W., 2008. Physical characterization 18

Page 18 of 22

382

of lansoprazole/PVP solid dispersion prepared by fluid-bed coating technique.

383

Powder Technol. 182, 480-485. Zhang, X., Wu, D., Lai, J., Lu, Y., Yin, Z., Wu, W., 2009. Piroxicam/2-hydroxypropyl-

385

beta-cyclodextrin inclusion complex prepared by a new fluid-bed coating

386

technique. J. Pharm. Sci. 98, 665-675.

ip t

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cr

387

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d

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an

us

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19

Page 19 of 22

388 389

Table and Figure legends

390 391 392

Table 1 Similarity factor (f2) for dissolution curves of SV/PVP solid dispersion in 0.2% SDS aqueous solution. Table 2 Contact angle values and water absorption rates of solid dispersions.

394

Figure 1 Instrument for water absorption rate test.

395

Figure 2 Dissolution of SV/PVP solid dispersions in 0.2% SDS.

396

Figure 3 Dissolution of SV/PVP solid dispersions in pure water (A.) and PBS (B.).

397

Figure 4 Relationship between DE and contact angle: critical contact angle(A.),

an

us

cr

ip t

393

SV/PVP solid dispersions (B.), and SDS incorporated SV/PVP solid

399

dispersions (C.).

401

Figure 5 Dissolution of SDS incorporated SV/PVP solid dispersions in water (A.), PBS (B.) and 0.2% SDS aqueous solution (C.).

d

400

M

398

Figure 6 Relationship between contact angle and water absorption rate.

403

Figure 7 Critical water absorption rate (A.) and relationship between DE and water

404 405

Ac ce pt e

402

absorption rate (B.) determined with SV/PVP solid dispersions.

20

Page 20 of 22

405 406

Table 1 Similarity factor (f2) for dissolution curves of SV/PVP solid dispersion in

407

0.2% SDS aqueous solution.

1/3.3

1/3.5

1/3.6

1/3.7

1/3.8

50.96

41.12

45.96

42.89

37.68

35.12

16.54

18.06

12.68

11.43

58.79

58.79

54.81

49.34

46.02

19.36

21.23

15.25

13.69

63.91

65.82

67.39

62.48

22.92

25.17

18.26

16.45

77.12

59.96

52.93

24.64

17.71

16.00

Ac ce pt e

1/3.7

d

1/3.6

62.86

1/3.8

1/3.9 408

1/4.0

56.39

23.54

25.67

18.55

16.71

76.53

25.41

28.04

20.14

18.26

26.26

29.05

20.97

19.00

66.85

50.77

44.11

44.47

39.80

M

1/3.4 1/3.5

22.57

1/3.9

ip t

1/3.4

cr

1/3.2

1/3.3

us

1/3.1

1/3.2

an

1/3.0

1/3.1

59.11

21

Page 21 of 22

cr us an

409

Table 2 Contact angle values and water absorption rates of solid dispersions. SV

water absorption rate (μL/min)

27.5±2.62

0.67±0.15

0.22±0.10

SDS incorporated solid dispersion

1/2.4

1/2.8

1/3.0

1/3.2

1/3.6

1/4.0

0.5%

1.0%

1.5%

62.1±7.97

56.1±2.43

54.0±3.83

48.4±1.35

40.6±1.77

40.2±1.14

37.5±1.63

48.8±1.05

40.6±1.25

37.5±2.07

0.35±0.03

0.50±0.10

0.55±0.10

0.56±0.05

0.61±0.07

0.64±0.09

0.80±0.11

0.95±0.03

0.67±0.15

0.33±0.02

Ac

ce

pt

411

67.0±1.13

SV/PVP solid dispersions

1/2.0

ed

contact angle

PVP

M

410

22

Page 22 of 22