Design of orthopedic support material containing diclofenac sodium microparticles: preparation and characterization of microparticles and application to orthopedic support material

Abstract

The aim of this study is preparation and characterization of diclofenac sodium microparticles and their application to the orthopedic support materials. The microparticles were obtained using spray drying method involving ethyl cellulose as shell material. The morphology, particle size, drug loading capacity and in vitro release characteristics of the drug microparticles were optimized for impregnation diclofenac sodium microparticles onto the orthopedic support materials. Scanning electron microscopy (SEM) was used to characterize the drug microparticles and the treated fabrics with microparticles. SEM images illustrated that the microparticles were spherical in shape and also fixed onto the orthopedic support materials. Furthermore, the resistance of materials containing microparticles to washing were also investigated. Finally, in vitro drug release studies of microparticles and textile impregnated with microparticles were done. This study suggested that textile systems containing diclofenac sodium microparticles could have a potential for long-term therapy for rheumatic disorders.

Keywords

Microencapsulation spray drying diclofenac sodium orthopedic support materials

In recent years, functional textiles used in medical and related healthcare have become an important and rapidly growing segment of the textile field.¹ The textile industry, together with medical knowledge, has paved the way for enriching the use of textile fabrics because of their interaction with the skin.² Textile materials have found uses in the medical field, for example as artificial aortas and bandages. However, advanced functional textile drug delivery systems were not developed until the end of the last millennium.³

Orthopedic support materials are used for protection and as support joints in various zones of the body. General examples of such applications are knee supports, wrist supports, ankle supports, elbow supports, shoulder supports and back supports. These supports are used for cure or protection. Medical applications usually happen in the areas listed below:

after operation or traumatic irritations;

in joint illnesses that are degenerative and inflammatory;

over-forced ligaments and tendons;

special problems of various joints.⁴

Transdermal drug delivery systems (TDDSs), in comparison to conventional pharmaceutical dosage forms, offer many advantages, including improved systemic bioavailability of active pharmaceutical ingredients, fewer administration frequency, longer duration of therapeutic action, reduction of side effects, steady drug delivery profile, etc.⁵ Several technologies have been developed and used in preparing TDDSs, and one of these is the use of medicated textiles for delivering drugs to specific body sites.⁶

Recently, microencapsulation has become an active field in textile science research as patent applications are increasing. The major interest in the microencapsulation process is currently in the application of durable fragrances, phase-change materials, dyes, fire retardants, counterfeiting and antimicrobial agents.⁷ This technique can also be used as an encapsulation method when it entraps active material within a protective matrix, which is essentially inert to the material being encapsulated.⁸

Polymers are frequently used in microencapsulation studies. Ethylcellulose is a water-insoluble polymer widely used in oral and topical pharmaceutical formulations.⁹ It is especially used to prepare sustained-release medications of various types. In the absence of polymer swelling ability, ethylcellulose becomes a key factor in such systems, because release kinetics would depend largely on the porosity of the hydrophobic compact.¹⁰

Spray-drying encapsulation, which was used particularly for the preparation of microparticulate drug delivery systems, has a number of advantages. It is a well-established technology, involving readily available equipment and comparatively low-cost encapsulation.¹¹ This technique transforms liquid feed into dry powder in one step, which is feasible for the scaling-up of the microencapsulation, continuous particle processing operation and can be used for a wide variety of materials.¹²

Diclofenac sodium (DS), a sodium salt of 2-[(2,6- dichlorophenyl)aminophenyl]-acetic acid (Figure 1), is a non-steroidal anti-inflammatory drug (NSAID), commonly used for the long-term treatment of rheumatic disorders, such as osteoarthritis, rheumatoid arthritic and ankylosing spondylitis.¹³ Several unwanted adverse effects are generally associated with the long-term oral administration of NSAIDs, including stomach ulcerations, abdominal burning, pain, cramping, nausea, gastritis and even serious gastrointestinal bleeding and liver toxicity. The DS is completely absorbed following oral administration, but its elimination half-life is relatively short (1–2 h). Due to its biopharmaceutical and pharmacological properties, sustained-release formulations of DS are desirable that should maximize therapeutic benefit and reduce the unwanted side effects, since the frequency of administration is lower, improving the therapeutic efficacy and patients’ compliance.^14–19

Figure 1.

Chemical structure of diclofenac sodium.

The aim of this study is the preparation and characterization of DS microparticles and their application to orthopedic support materials. The microparticles were obtained using the spray-drying method involving ethyl cellulose as a matrix material to control drug release. The morphology and particle size of the drug microparticles were optimized for impregnation of DS microparticles onto the orthopedic support materials. Finally, in vitro drug-release studies of microparticles and textile impregnated with microparticles were done.

Materials and methods

Materials

DS (CAS Number: 15307-79-6), acquired from Amoli Organics, India, was the active material used. Aqueous formulations based on ethyl cellulose (Surelease® E-7-19040, fully plasticized aqueous ethylcellulose dispersion with 25% (w/w) solid content, Colorcon, England) were used as controlled release polymeric system. The polymers were blended with the excipients propylene glycol (Sigma, USA), as a plastifying agent, colloidal silicon dioxide (Cab-O-Sil® M5, Cabot Corp., Germany), as a glidant, and distilled water.

A textile fabric composed of wool, acrylic, polyester and elastane was used as orthopedic support material, supplied by Interfarma (Turkey). For the impregnation of the textile fabrics with microparticles using the foulard, the aqueous bath was prepared by adding microparticles and nano-dispersion of a polyether polyurethane self-cross-linking agent (Baypret Nano-PU, Tanatex Chemicals, the Netherlands). The mentioned nanodispersed polyether polyurethane was obtained by dispersing to a particle size of less than 100 nm The general properties of this agent are amphoteric/anionic, yellowish liquid, 1.10 g/cm³ density, 50 mPas viscosity, pH 4.5–5.5 at 20℃ and miscible in water.²⁰

Methods

Preparation of microparticles

The microencapsulating runs were carried out in a bench-top spray dryer model SD-04 (Lab-Plant, North Yorkshire, England), with concurrent flow regime. Aqueous dispersion of ethyl cellulose (Surelease®) was used as controlled release polymeric system. DS and the polymer dispersion were suspended in distilled water. The drug:polymer ratios in the microencapsulating compositions were maintained at 1:1, 1:2 and 1:4 (dry base). Propylene glycol at concentrations of 0.6% and 0.75% w/w of colloidal silicon dioxide were then added to the drug/polymer suspension and maintained under agitation for 30 min. The starting compositions of formulations in spray drying are shown in Table 1. The resulting compositions were then fed to the spray dryer under the following conditions: feed flow rate of the microencapsulating composition, Ws, 10 g/min; inlet air temperature, Tai, 125℃ and outlet air temperature Tao, 60–66℃. Samples of the spray-dried microparticles were collected during the experiments. Microparticles prepared were subjected to physical and chemical characterization.

Table 1.

Contents of syray drying formulations (for 250 g)

Drug:polymer ratio Content (g)	1:1	1:2	1:4
Diclofenac sodium	7.5	3.75	1.875
Surelease®	39.267	39.267	39.267
Propylene glycol	1.5	1.5	1.5
Colloidal silicon dioxide	1.875	1.875	1.875
Distilled water	199.86	203.608	205.483

Characterization of the microparticles

The effects of spray-drying conditions and composition of the microencapsulating formulation on physical and chemical properties of DS microparticles were assessed by determining drug content and encapsulation efficiency, particle size and size distributions, particle morphology, Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) and powder X-ray diffractometry (XRD) analysis.

Drug content and encapsulation efficiency

The DS content of microparticles was determined spectrophotometrically. Phosphate buffer solution (5 ml; pH 7.4) was added on 20 mg of microparticles and shaken for 23 h. Then, 5 ml of buffer solution was added and it was shaken for another 1 h. After filtration, 0.1 ml of filtrate was diluted to 10 ml with buffer solution. The absorbance of the solution was measured at 276 nm by a spectrophotometer against the blank, and drug concentration was determined from the calibration curve (n = 5). Encapsulation efficiency for each formulation was determined by using following equation:

\begin{matrix} Encapsulation efficiency, ɛ (%) \\ = \frac{total amount of DS loaded experimentally}{total amount of DS loaded theoretically} \times 100 \end{matrix}

(1)

Particle size and size distributions

The particle size and size distributions of the microparticles were measured by laser diffractometer (Malvern-Mastersizer 2000) using a dry powder feeder. The particle sizes were expressed as the mean diameter over the volume distribution, d4.3, and the size distributions (span) were calculated using following equation:

span = \frac{[d (0.9) - d (0.1)]}{d (0.5)}

(2)

where d_0.1, d_0.5 and d_0.9 are, respectively, the particle diameters at 10%, 50% and 90% of the undersized particle distribution curve.

Particle morphology

The morphology of the spray-dried microparticles was evaluated through scanning electron microscopy (SEM), using a JEOL electron microscope (Tokyo, Japan) at 15 kV. Powder samples were attached to double-sided adhesive carbon tabs mounted on the microscope support, and coated with a thin layer of the gold, using an ion sputter JEOL JFC 1100 device. Measurements were taken in vacuum at different magnifications.

Fourier transform infrared spectroscopy

FT-IR spectra of the samples were obtained using a Perkin Elmer Spectrum 100 FT-IR spectrometer (Perkin Elmer Spectrum 100, Massachusetts, USA) at room temperature, with wavenumbers ranging from 4000 to 650 cm⁻¹, using four scans with a resolution of 4 cm⁻¹.

Differential scanning calorimetry

The DSC of DS and microparticles was performed using a DSC Q100 V9.0 Build 287 (TA Instruments, USA) equipped with thermal analysis data acquisition software. The instrument was calibrated with indium. All the samples (between 4 and 5 mg) were heated in aluminum pans using dry nitrogen as the effluent gas. The analysis was performed with a heating range of 40–320℃ and at a rate of 20℃/min.

X-ray powder diffractometry

X-ray diffraction patterns of pure drug and microparticles were obtained with a Rigaku X-ray diffractometer equipped with a personal computer for data acquisition and analysis in the 2 θ range between 3° and 90° using CuKα-radiation (40 kV; 36 mA). Samples were mildly pre-ground with a pestle in an agate mortar to make them homogeneous, in order to control crystal size and to minimize preferred orientation effects.

Impregnation of microparticles on orthopedic support material

Microparticles were applied to orthopedic support materials at a laboratory scale; this application method can easily be applied in any textile finishing factory. Microparticles were applied in the finishing process of textile fabrication using a foulard, in which the textile to be treated is impregnated using a finishing bath containing (i) microparticles and (ii) a nano-dispersion polyether polyurethane self-cross-linking agent. The conditions required for this procedure are shown in Table 2. The pick-up (expressed in %) is just the ratio:

Pick Up (%) = \frac{(\begin{matrix} mass of wet textile after pad - \\ mass of dry textile \end{matrix})}{mass of dry textile} \times 100

(3)

Table 2.

Conditions of textile impregnation process

Finishing conditions
Substrate	Orthopedic support material
Process	Foulard
Pick-up (%)	98
Microparticles	40 g/l
Nano-dispersion of polyether polyurethane self-cross-linking agent	40 g/l
Drying conditions	100℃, 2 h
Thermofixing conditions	130℃, 10 min

Scanning electron microscopy of textile impregnated with microparticles

Impregnated textile and washed samples were coated with a thin layer of sputtered gold prior to examination, using an ion sputter JEOL JFC 1100 device. Samples were observed using a JEOL scanning electron microscope (Tokyo, Japan) at 15 kV.

Air permeability test

Air permeability of textile materials was measured, according to ISO 9237:1995 Textiles: Determination of the Permeability of Fabrics to Air, using a Textest FX 3300 Air Permeability Tester.²¹

Laundering test

To test laundering durability, specimens were treated on a short time program in an Atlas Linitest for 30 min at 30°C, in accordance with ISO 105 C06: Color fastness to domestic and commercial laundering ²² At the end of the cycle, samples were dried at room conditions. All samples were examined after 10 and 20 cycles.

In vitro drug-release studies

DS microparticles

Spray-dried microparticles equivalent to 20 mg of DS were suspended in glass vessels containing 100 ml of phosphate buffer solution (pH 7.4) and incubated on a shaking bath at 37°C, 70 rpm. At appropriate time intervals the solutions were withdrawn and the amount of DS released was evaluated spectrophotometrically at 276 nm.

Textile impregnated with DS microparticles

One gram (about 6 × 2.5 cm², which contained approximately 1% DS) of the textile impregnated with microparticles was suspended in glass vessels containing 100 ml of phosphate buffer solution (pH 7.4) and incubated on a shaking bed at 37°C, 70 rpm. At appropriate time intervals the solutions were withdrawn and the amount of drug released from the textile impregnated with microparticles was evaluated spectrophotometrically at 276 nm. Then an equal volume of the same release medium was added back to maintain a constant volume.

Differences among the release of three formulations (1:1, 1:2, 1:4) were performed using analysis of variance (ANOVA) followed by Tukey–Kramer multiple comparison tests for the first three hours. A student’s t-test was used for two formulations (1:2, 1:4) following 2 hours. Mean values (mean ± SEM) are presented Table 5 (GraphPad Instat™, 1990–1994, GraphPad Software V2.05a 9342, USA). For all studies, p values of <0.05 were considered to be statistically significant.

Results and discussion

Characterization of microparticles

Drug content and encapsulation efficiency

Higher encapsulation efficiency values were obtained for the microparticles composed of a drug:polymer ratio of 1:1, which are shown in Table 3. When the DS load of the microparticles was decreased from 36.82% to 10.77%, the encapsulation efficiency dropped from ∼94% to ∼77%.

Table 3.

Drug loading, encapsulation efficiency and particle size and distribution values

Formulation	Actual drug loading^a (%)	Encapsulation efficiency^a ɛ (%)	Particle size and distribution
Formulation	Actual drug loading^a (%)	Encapsulation efficiency^a ɛ (%)	d_0.1 (µm)	d_0.5 (µm)	d_0.9 (µm)	d_4.3 (µm)	Span
1:1	36.82 ± 2.51	93.42 ± 6.37	3.15	7.34	15.34	8.61	1.66
1:2	19.09 ± 0.53	77.76 ± 2.17	2.62	6.94	18.10	9.68	2.23
1:4	10.77 ± 0.40	76.98 ± 2.86	2.74	6.98	15.45	8.44	1.82

Values are mean ± S.E.

Particle size and size distributions

Particle size and distributions of the prepared microparticles are shown in Figure 2. The mean particle sizes of microparticles formed by (1:1), (1:2) and (1:4) formulations are 8.61, 9.68 and 8.44 µm with span values of 1.66, 2.23 and 1.82, respectively (Table 3).

Figure 2.

Particle size distributions of microparticles: (a) (1:1); (b) (1:2); (c) (1:4).

Particle morphology

Typical photomicrographs obtained by scanning electronic microscopy of spray-dried microparticles (1:1), (1:2) and (1:4) are shown in Figure 3. It can be seen in the figure that the spray-dried product is composed mainly of spherical-shape particles, and one can notice also the absence of agglomerates. They also indicate the formation of microparticles with homogeneous characteristics and smooth appearance, and do not show the presence of free drugs on the microparticles’ surfaces. In general, these morphological characteristics indicate that the drug is dispersed through the microparticles.

Figure 3.

Scanning electron photomicrographs of spray-dried microparticles: (a) (1:1); (b) (1:2); (c) (1:4).

Fourier transform infrared spectroscopy

Interaction between the drug and polymers is commonly brought about by identifiable changes in the FT-IR patterns.²³ FT-IR patterns of DS and microparticles are demonstrated in Figure 4. Characteristic peaks at 3387 cm^–1 as a result of N-H stretching of the secondary amine, 1572 cm^–1 due to –C = O stretching of the carboxyl ion and at 744 cm^–1 owing to C-Cl stretching were exhibited in FT-IR spectra of DS (Figure 4(a)). The FT-IR spectra of drug-free microparticles containing ethyl cellulose show an asymmetric peak at around 2973–2925 cm^–1, which is due to C-H stretching (Figure 4(b)). The peak at 1375 cm^–1 is due to CH3 bending and the small peak near 1450 cm^–1 is due to CH2 bending. The broad distinct peak near 1050 cm^–1 may be due to the C-O-C stretch in the cyclic ether. The peaks of DS-loaded microparticles (Figure 4(c)–(e)) were similar (but with lesser intensity) to the spectrum of DS. The peaks of various functional groups, as described in the IR spectrum of DS, were also present in the microparticles without any shift or change. These observations revealed the intact nature of the DS present in the microparticles. From these results, the absence of drug-polymer system interaction and the stability of the encapsulated drug in microparticles were confirmed. A similar type of observations with other drug/carriers was reported by Saravanan et al.²⁴ and Desai.²⁵

Figure 4.

Fourier transform infrared spectra of pure diclofenac sodium (a), 1:1 microparticles (b), 1:2 microparticles (c), 1:4 microparticles (d).

Differential scanning calorimetry

DSC thermograms of pure drug, drug-free microparticles and drug-loaded microparticles are displayed in Figure 5. The DSC thermogram of pure drug (Figure 5(a)) showed one endothermic peak. This sharp peak at 297.78℃ is due to melting of the drug. In the case of drug-free microparticles (Figure 5(b)), there was no defined peak. In the case of drug-loaded microparticles, small peaks were observed at 242.4, 98.41 and 100.37℃ in 1:1, 1:2 and 1:4 microparticles (Figure 5(c)–(e)), respectively. This indicated that the drug has the amorphous distribution in the polymer matrix. At the same time, these results also showed that there is no interaction between the drug and polymer systems. DSC results demonstrated consistency with the findings obtained from FT-IR analysis.

Figure 5.

Differential scanning calorimetry thermograms of diclofenac sodium (a), drug-free microparticles (b), drug:polymer ratio 1:1 microparticles (c), drug:polymer ratio 1:2 microparticles (d) and drug:polymer ratio 1:4 microparticles (e).

X-ray powder diffractometry

The physical nature of the drug entrapped in microparticles was further confirmed by X-ray diffraction studies. XRD patterns of drug, drug-free microparticles, microparticles, textile fabric and textile impregnated with microparticles are shown in Figure 6(a)–(e), respectively. It can be observed that the X-ray diffraction patterns of DS showed sharp peaks due to the crystalline nature of the drug. However, these drug peaks disappeared in the X-ray diffraction patterns of microparticles and the textile impregnated with microparticles (Figure 6(c) and (e)). It was thought that the DS showed its specific crystal peaks when it existed in a crystalline form, but after the drug was entrapped in the microparticles, it could exist as a molecular dispersion. Saravanan et al.²⁴ and Desai²⁶ observed similar patterns with other drug/carriers. This, in support of the DSC study, clearly reveals the amorphous form of entrapped drug in the microparticles. A phase change often occurs during the spray-drying process and it may lead to the production of amorphous substances.²⁷

Figure 6.

X-ray diffraction patterns of diclofenac sodium (a), drug-free microparticles (b), microparticles composed of a drug:polymer ratio of 1:1 (c), textile fabric (d) and textile fabric impregnated with microparticles composed of a drug:polymer ratio of 1:1 (e).

Scanning electron microscopy of textile impregnated with microparticles

Textile materials were analyzed by SEM after being impregnated with microparticle dispersions. SEM photomicrographs confirmed that the adhesion between textile fiber and microparticles was effective, as can be observed in Figure 7. Using SEM (Figures 7 and 8), it can be determined that the microparticles are a spherical shape between fibers.

Figure 7.

Scanning electron photomicrographs of textile impregnated with microparticles.

Figure 8.

Scanning electron photomicrographs of textile impregnated with microparticles washed for (a) 10 cycles (b) 20 cycles in accordance with standard ISO 105 C06.

Air permeability test

The air permeability test is one of the major properties of textile materials and is governed by factors such as the fabric structure, density, thickness, surface characteristics, etc. The air permeability test was performed to determine the effect of microparticles on the air permeability properties of textile materials. The air permeability results of textile materials impregnated with microparticles is shown in Table 4. According to the results, the air permeability value of the textile impregnated with microparticles was slightly decreased. This was because the microparticles fill in the space between fibers. When concentrations of microparticles and the cross-linker on orthopedic support material are kept constant, the air permeability values of the orthopedic support material impregnated with microparticles are not expected to change. This is also confirmed with the air permeability results given in Table 4. There is no significant difference between the air permeability values of the textile materials impregnated with microparticles prepared in different drug:polymer ratios. However, due to the fact that cross-linking material forms cross-links and that it is a nano-sized coating material, the air permeability values were observed to decline when compared with values of untreated orthopedic support material.

Table 4.

The air permeability values of textile materials impregnated with microparticles

Sample	Air permeability value (mm/s)
Untreated orthopedic support material	226
Orthopedic support material impregnated with microparticles composed of a drug:polymer ratio of 1:1	199.5
Orthopedic support material impregnated with microparticles composed of a drug:polymer ratio of 1:2	198
Orthopedic support material impregnated with microparticles composed of a drug:polymer ratio of 1:4	198.5

Laundering test

The SEM photomicrographs of textiles containing microparticles that were washed 10 and 20 times are shown in Figure 8. It can be observed that microparticles remained on textiles after the application of washing cycles. Even after 20 washing cycles some drug-loaded microparticles still remained on the fabric. The results showed that the microparticles were not adsorbed on the surface of textile, but absorbed by textile material in the presence of the self-cross-linking agent and bindings between microparticles and fibers were durable against 20 launderings.

In vitro drug-release studies

DS microparticles

Figure 9 shows the amount of drug released from microparticle formulations. In vitro release study of the microparticles showed that the time for 100% DS release was extended to 90, 120 and 150 min for 1:1, 1:2 and 1:4 microparticle formulations, respectively, when compared to 60 min for pure DS. The results indicate that increasing the polymer ratio decreased the release rate. In the drug-release medium, all microparticle formulations showed an initial fast release due to the dissolution of the drug from the surface, but the release of the drug was extended up to 150 min depending on the polymer ratio. As more drug is released from the microparticles, more channels are probably produced, contributing to faster drug-release rates. In addition, higher drug levels in the microparticle formulation produced a higher drug concentration gradient between the microparticles and drug-release medium; thus, the drug-release rate was increased.

Figure 9.

In vitro diclofenac sodium (DS) release profiles from pure drug and microparticles.

Textile impregnated with DS microparticles

The results of the in vitro release of textile impregnated with microparticles with different drug:polymer ratios in pH 7.4 phosphate buffer solutions at 37℃ are presented in Figure 10. It can be seen that at the beginning of the drug-release study, for all formulations, a larger amount of DS was freed from the surface of the textile (about 60–90%). This fast release may be attributed to the small size of the microparticles (8.44–9.68 µm) and the vast surface area and amorphous characteristics of drug. Amorphous drugs have different physiochemical properties and are more soluble than the crystalline drugs²⁸. Therefore, fast dissolution of the encapsulated drug could take place immediately when the drug particle was exposed to the aqueous environment. A burst effect was exhibited in all drug-release profiles at the first hour⁶. Since DS is soluble in pH 7.4 phosphate buffer solution, the burst effect is probably caused by the fast dissolution of the drugs located close to the surface of the microparticles. The dissolution of the surface drug will result in channels, allowing the aqueous medium to penetrate into the matrix, leading to drug dissolution and subsequent drug release via the medium-filled channels. A possible explanation for this phenomenon is that a significant loading of drug is located in the vicinity of the microparticle surface, and this is released as the cavity size increases.

Figure 10.

In vitro diclofenac sodium release profiles of textiles impregnated with microparticles.

After 1 hour, there was a steady release of drug into the release medium for all formulations. When we compare the formulations with each other, the drug-release ratio was higher in 1:1 than in 1:2 and 1:4 in the first three hours (p < 0.001 for each point) Drug release was completed in the third hour in formulation 1:1 and was completed in the fifth hour in formulation 1:2. Completion of the drug release in formulation 1:4 was longer than eight hours. In formulation 1:2, drug release was higher than in formulation 1:4 in the fourth and fifth hours (p < 0.001 and p < 0.0001, respectively; Table 5). As a result, it can be implied that the increase of drug loading caused a more rapid drug release. Polymer concentration and drug-release behavior were directly proportional.

Table 5.

Statistical analysis of release studies

Formulations
Time (h)	1:1	1:2	1:4
1	88.8 ± 1.8***###	71.5 ± 1.1†††	59.5 ± 0.8
2	98.4 ± 0.8***###	86.7 ± 0.7†††	79.9 ± 0.6
3	100.0 ± 0.0***###	93.9 ± 0.1†††	86.9 ± 0.9
4	98.5 ± 0.4†††	90.5 ± 0.4
5	100.0 ± 0.0††††	91.6 ± 0.3
7	95.4 ± 0.8
8	97.5 ± 0.8

***

p < 0.001 (1:1 versus 1:2), ###p < 0.001 (1:1 versus 1:4), †††p < 0.001 (1:2 versus 1:4), ††††p < 0.0001 (1:2 versus 1:4)

To determine the mechanism of drug release, 1:2 and 1:4 microparticles and textiles impregnated with 1:2 and 1:4 microparticles, which have prolonged drug release, were subjected to release kinetic studies; their respective r² values are given in Table 6. As indicated (Table 6) by the higher correlation coefficient (r²), the drug release from microparticles and textile-impregnated microparticles followed the first-order equation (concentration-dependent release of drug) rather than the Higuchi kinetic model (diffusion-controlled release of drug).

Table 6.

Correlation coefficient value (r²) of microparticles and textile impregnated with microparticles

Higuchi	First order
Formulation	r ²	r ²
1:2 Microparticles	0.925	0.967
1:4 Microparticles	0.935	0.939
Textile impregnated with 1:2 microparticles	0.970	0.975
Textile impregnated with 1:4 microparticles	0.840	0.967

Conclusions

In this study, DS microparticles were successfully prepared using a spray-drying method that included aqueous dispersion of ethyl cellulose. Morphology, size and size distribution, FT-IR spectroscopy, DSC, X-ray studies on microparticles and laundering behavior of microparticles from textiles were assessed. Microparticles were seen to be spherical and smooth in structure, with a mean diameter in the range of 8.44–9.68 µm. The amorphous nature of entrapped DS in microparticles was confirmed by the DSC and XRD studies.

The microparticles were applied in the finishing process of textile fabrication using a foulard, in which the textile to be treated is impregnated using a finishing bath containing (i) microparticles and (ii) a self-cross-linking agent. The surface morphology of microparticles has been studied by means of SEM. It can be observed that microparticles containing DS remain on the orthopedic support material after 10 and 20 washing cycles. The difference between the air permeability values of the textile materials impregnated with microparticles prepared in different drug:polymer ratios was observed to be not significant. According to the in vitro release studies, the increase of drug loading caused a more rapid drug release, and polymer concentration/drug-release behavior were directly proportional.

The orthopedic textile material prepared by our system could be developed further into a medical textile that has the potential to provide a TDDS after many launderings.

Footnotes

Acknowledgements

We acknowledge Professor Dr Ufuk Yücel, Ege Vocational Training School, Ege University, for allowing us to use the spray-drying equipment.

Funding

This work was supported by the Scientific and Technological Research Council of Turkey (TÜBİTAK; Project Number 109M272) and the Scientific Research Department of Dokuz Eylul University (Project No: 2009.KB.FEN.019). We are grateful to the financial support from TÜBİTAK and the Scientific Research Department of Dokuz Eylul University.

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