Application of solid dispersion technique in improving solubility of ibuprofen by poloxamers

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1 Research Article ISSN: Md. Abdullah Al Masumet al. /BioMedRx 2013,1(5), Available online through Application of solid dispersion technique in improving solubility of ibuprofen by poloxamers Md. Abdullah Al Masum 1, Florida Sharmin 2, Rezaur Bin Islam 1, Md. Ariful Islam 1 and S. M. Ashraful Islam 2, * 1 Research & Development Formulation Department, Incepta Pharmaceuticals Ltd, Savar, Dhaka, Bangladesh. 2 Department of Pharmacy, University of Asia Pacific, Dhanmondi, Dhaka-1209, Bangladesh. Received on: ; Revised on: ; Accepted on: ABSTRACT Primary objective of the current study was to formulate solid dispersion (SD) systems of practically water insoluble drug, Ibuprofen with Poloxamer. SDs with Poloxamer 188 and Poloxamer 407 at three different ratios (1:0.5, 1:1 and 1:1.5) were prepared by melt dispersion and solvent evaporation techniques. Effect of different methods on solubility properties and the efficacy of the carriers to improve the dissolution characteristics were evaluated and compared. Drug carrier interactions in the prepared solid dispersions (SDs) were investigated by FT-IR spectroscopy and DSC thermal study. Drug-carrier physical mixtures were also prepared in the same ratio of SDs to compare the dissolution behavior. The obtained solid dispersions (SDs) were tested for drug content, saturation solubility and drug dissolution. Saturation solubility study of the SDs was carried out in phosphate buffer (ph 7.2), 0.1 N HCl solution and distilled water. Solid dispersions (SDs) were found to improve the aqueous solubility of Ibuprofen up to 14 times. Dissolution test was performed in phosphate buffer (ph 7.2) and in 0.1 N HCl. Data obtained from the studies showed significant enhancement of the release rate and extent of Ibuprofen from the solid dispersions. Selective SDs were filled into hard gelatin capsule shells and the release characteristics of the capsules were also investigated. Drug release from capsules was also found higher than the pure drug. Key words: Solid Dispersion, Ibuprofen, Solubility, Poloxamer 188 and Poloxamer INTRODUCTION Ibuprofen is (2RS)-2-[4-(2-Methylpropyl) phenyl] propanoic acid, the most commonly used and most frequently prescribed NSAID. 1 It is an essential non-steroidal anti-inflammatory drug characterized with poor aqueous solubility. It is practically insoluble in water, having pka of Therefore, dissolution of ibuprofen is a rate limiting step that sometime results in incomplete absorption due to poor dissolution and/or delayed dissolution. But rapid onset of action is vital for pain situations particularly in dental pain, rheumatoid and osteoarthritis and breast cancers. To improve the solubility characteristics followed by dissolution of such drug is thus challenging and rational. (2RS)-2-[4-(2-Methylpropyl) phenyl] propanoic acid *Corresponding author. S. M. Ashraful Islam Department of Pharmacy, University of Asia Pacific, Dhanmondi, Dhaka-1209, Bangladesh. The solid dispersion (SD) technique is one of the most widely applied technologies for solving the bioavailability problems of poorly aqueous soluble drugs in recent years. The technology overcomes the limitations of conventional methods for reducing particle size and increasing bioavailability. 4 Solid dispersion refers to a group of solid products consisting of at least two different components, generally a hydrophilic matrix and a hydrophobic drug. 5 The matrix can be either crystalline or amorphous or blended mixture. The drug can be dispersed up to molecular level and hence, solubility is increased as a result of enhanced wettability. It is the mean of reducing particle size and the drug can be dispersed molecularly in amorphous particles (clusters) or in crystalline particles. 6, 7 Various researchers have reported to use solid dispersion technique to increase the solubility and dissolution behavior of Ibuprofen remarkably by using various water soluble carriers. PVP,HPMC, Eudruagit and PEG , mannitol 9, Poloxamer 407 and Poloxamer 407 micro 10, sodium lauryl sulphate 11 have been used to improve the dissolution characteristics of Ibuprofen significantly. In this study, we attempted to improve the solubility of Ibuprofen by solid dispersion technique where water soluble Poloxamer 188 and Poloxamer 407 were used as carriers. The solid dispersions were prepared in 1:0.5, 1:1 and 1:1.5 ratios by melt dispersion and solvent evaporation method. The effect of different methods on solubility of drug and the efficiency of the carrier to improve the solubility and dissolution charac-

2 Md. Abdullah Al Masumet al. /BioMedRx 2013,1(5), teristics were evaluated and compared. The prepared solid dispersions were also tested for compatibility by FT-IR and DSC thermograms, drug content, saturated and phase solubility. Finally hard gelatin capsules were prepared from the obtained SDs and in vitro release from the capsules were also evaluated. 2.MATERIALS AND METHODS 2.1. Materials Poloxamer 188 and Poloxamer 407 were obtained from Incepta Pharmaceuticals Ltd, Bangladesh as kind gifts. Ibuprofen was collected from ACI Pharmaceuticals Ltd, Bangladesh. All other ingredients were of analytical grade and collected from local market Preparation of SDs by Melt Dispersion Technique Solid dispersions were prepared by melt dispersion (MD) method using Poloxamer 188 and Poloxamer 407 as carrier. The SDs were prepared at weight ratio of 1:0.5, 1:1, 1:1.5 (drug: carrier) and coded as per Table 1. The required amount of carrier and ibuprofen were melted in a beaker on a water bath maintained at 80 0 C and mixed thoroughly with a glass rod for 5 min. The mixture was cooled rapidly by placing the beaker in an ice bath for 5 min to solidify, then powdered in a mortar, sieved through an 18 mesh screen and kept in a screw-cap vial at room temperature and stored in desiccators for further use Preparation of SDs by Solvent Evaporation Method Solvent evaporation (SE) method was also used to prepare solid dispersions with same carriers in same weight ratio and coded as per Table 1. The required amount of carrier and ibuprofen were dissolved in 10 ml of methanol in a beaker and stirred thoroughly with a glass rod for 5 min. The solution was then evaporated at room temperature for 24 hours. The solidified mass was then powdered in a mortar, sieved through an 18 mesh screen and kept in a screw-cap vial at room temperature and stored in desiccators Preparation of Physical Mixture (PM) The physical mixtures (PM) in the same weight ratio as the solid dispersions mentioned above were prepared by thoroughly mixing the appropriate amounts of ibuprofen and carrier for 10 min in a mortar. The mixtures were coded as per Table 1. The mixtures were sieved through an 18 mesh sieve and stored in screw-cap vials at room temperature and used for further study Drug Content Analysis To assess the mixing uniformity of drug in the solid dispersions, Ibuprofen standard sample and equivalent solid dispersions were dissolved in methanol separately. Methanol is chosen as the diluting solvent as ibuprofen is very soluble in methanol. 6 The standard and sample solutions were suitably diluted by methanol and absorbance was measured by using a UV Spectrophotometer (UV mini 1240, Shimadzu) at 221 nm. The assay procedure was repeated thrice and standard deviation was calculated to see the uniformity Solubility Studies Solubility studies of pure Ibuprofen and solid dispersions were car ried out in three different media; 0.1 N HCl solution, phosphate buffer (ph 7.2) and distilled water. Ibuprofen and samples of solid dispersions equivalent to 100 mg of pure drug were taken in 15 ml screw cap test tubes containing 10 ml of media. The solutions were shaken for 24 hrs with continuous stirring. After 24 hrs, the sample solutions were filtered through Whatmann filter paper and the filtrate was diluted to a suitable concentration with respective media. The absorbance of the prepared dilutions was measured at 221nm using UV- Visible spectrophotometer. The dissolved amount of drug was calculated from the standard curves for 0.1 N HCl and 7.2 phosphate buffer and from the absorbance of the standard solution at aqueous media Drug-Carrier Interactions Study by FT-IR FT-IR spectra were taken by IR-Prestige 21, Shimadzu, Japan by scanning the sample in potassium bromide (KBr) discs. Before taking the spectrum of the sample, a blank spectrum of air background was taken. The sample of pure drug, pure polymers and the solid dispersions containing both the drug and polymer were scanned over the frequency range 2000 cm -1 to 400 cm -1. The IR spectra of solid dispersions were compared with standard IR spectra of pure Ibuprofen and respective carrier Differential Scanning Calorimetric (DSC) Studies DSC analysis of the drug, carrier and their solid dispersions were carried out in Bangladesh Council of Scientific and Industrial Research (BCSIR). Samples were heated under nitrogen atmosphere on an aluminum pan at a rate of 10 C/min over the temperature range of 30 C and 300 C. Thermal data analysis of DSC thermogram was conducted by using STAR software In Vitro Dissolution Studies The in vitro dissolution studies were carried out by USP XXII six stage dissolution test apparatus using 900 ml of dissolution medium. Two dissolution media were used in the study; phosphate buffer ph 7.2 as recommended by USP-33 for ibuprofen tablet and 0.1 N HCl as suitable medium for immediate release solid dosage forms. 200 mg of Ibuprofen or its equivalent samples were placed in the dissolution medium. Paddle was used at a stirring rate of 50 rpm at a constant temperature of 37 0 C± C. A 5 ml aliquot was withdrawn at predetermined time intervals of at 5, 10, 20, 30, 45 and 60 minutes and diluted suitably with dissolution medium and the absorbances were measured at 221nm using Shimadzu UV-1201 UV/Visible double beam spectrophotometer (Shimadzu, Japan). Fresh dissolution medium was replaced immediately to maintain the volume constant. Percent drug release was calculated using the equation obtained from the standard curve prepared in each media. To characterize the drug release rate in different experimental conditions, MDT (mean dissolution time), T 50%, T 80% and percent dissolution efficiency (DE) were calculated from dissolution data according to the following equations 12. T 50% = (0.5/k) 1/n T 80% = (0.8/k) 1/n MDT = (n/n+1). K -1/n

3 Md. Abdullah Al Masumet al. /BioMedRx 2013,1(5), in a room of controlled temperature and humidity. The filled capsules were then kept in glass vials and stored in desiccators in room temperature for further use. Where k is the antilog of intercept & n is a release exponent of Korsmeyer s plot and y is the percentage of dissolved drug. Mean dissolution time (MDT) value is used to characterize the drug release rate from the matrix. A higher value of MDT indicates a lower drug releasing ability of the solid dispersion and vice-versa. Besides, The DE is the area under the dissolution curve up to a certain time t, expressed as a percentage of the area of the rectangle described by 100% dissolution in the same time. Larger the value of DE, higher is the dissolution rate Preparation of Capsules SD of 1:1 ratio prepared by melt dispersion and solvent evaporation technique was used to prepare capsules. 100 mg of pure Ibuprofen and SD equivalent to 100 mg (as per found potency in Table 1) for each capsule were weighed accurately by the Sartorious electronic balance and filled in 0 size shell. The capsule filling was performed Evaluation of Capsules The prepared capsules were tested for in vitro disintegration test. Three capsules from each batch were tested for disintegration time by Electrolab disintegration tester ED-2L at 37 o C±0.5 o C. Six capsules from each batch underwent in vitro dissolution study by using above stated method in phosphate buffer (ph 7.2). 3. RESULTS AND DISCUSSION The primary objective of the study was to increase the dissolution rate of ibuprofen; a poorly water soluble drug. Poloxamer 188 and Poloxamer 407 in different ratio were used to prepare SDs and PMs for this purpose. All the solid dispersions prepared by melt dispersion and solvent evaporation technique were found to be granular, fine and free flowing. Solid dispersions prepared by melt dispersion technique were found more granular and non-sticky than those prepared by solvent evaporation for both of the two carriers. Drug content analysis yielded results from 95% to 102% of the theoretical claim. The results are summarized in Table 1. Table 1- Code names and results of drug content analysis of SDs and PMs of Ibuprofen. Sl. No. D:C Ratio Carrier Preparation Code Theoretical Calculated drug content (%) drug content (%) 1 1:0.5 Poloxamer 188 Solid dispersion by melt dispersion ½ MD 66.7% 65.9% 2 1:1 1 MD 50.0% 48.9% 3 1:1.5 1½ MD 40.0% 39.6% 4 1:0.5 Solid dispersion by solvent evaporation ½ SE 66.7% 65.4% 5 1:1 1 SE 50.0% 49.1% 6 1:1.5 1½ SE 40.0% 39.0% 7 1:0.5 Physical mixture ½ PM 66.7% 66.1% 8 1:1 1 PM 50.0% 48.7% 9 1:1.5 1½ PM 40.0% 39.2% 10 1:0.5 Poloxamer 407 Solid dispersion by melt dispersion ½ MD 66.7% 65.7% 11 1:1 1 MD 50.0% 49.3% 12 1:1.5 1½ MD 40.0% 39.6% 13 1:0.5 Solid dispersion by solvent evaporation ½ SE 66.7% 66.1% 14 1:1 1 SE 50.0% 49.2% 15 1:1.5 1½ SE 40.0% 40.1% 16 1: 0.5 Physical mixture ½ PM 66.7% 66.5% 17 1:1 1 PM 50.0% 49.8% 18 1: 1.5 1½ PM 40.0% 39.4% D:C ratio- Drug : carrier ratio, P1- Poloxamer 188, P4- Poloxamer 407, MD- melt dispersion, SE- solvent evaporation, PM- physical mixture, ½- ratio 1:0.5, 1½ratio 1:1.5.

4 Md. Abdullah Al Masumet al. /BioMedRx 2013,1(5), 3.1. Result of saturation solubility The saturated solubility of ibuprofen and solid dispersions were investigated in three media; 0.1 N HCl, phosphate buffer ph 7.2 and distilled water. Saturation solubility study of solid dispersions using Poloxamer 188 and Poloxamer 407 were found effective in enhancing solubility in all the three media. In most of the cases, SDs made of melt dispersion technique showed higher solubility than those prepared by solvent evaporation method. In a similar fashion, higher solubility was obtained on addition of more polymers in the dispersion for most of the cases except some exceptions. Poloxamer 407 clearly rendered the drug more soluble in all three media irrespective to the preparation method. At 1:1.5 ratio, solid dispersion with Poloxamer 188 made of melt dispersion technique showed a saturated solubility of mg per ml of 0.1 N HCl, whereas solid dispersion with Poloxamer 407 made of same method showed mg per ml. Similar increase of solubility were found in other two media and also for the solid dispersions made of solvent evaporation technique. Solubility was enhanced up to folds in distilled water by ½ MD, 1.65 folds in 7.2 Phosphate buffer by P4 1½ SE and 6.55 folds in 0.1 N HCl by P4 1½ MD. Results of saturation solubility study have been summarized in Table 2. Table 2- Saturated solubility of ibuprofen and solid dispersions in 0.1 N HCl, Phosphate buffer ph 7.2 and distilled water. Name 0.1 N HCl 7.2 Phosphate Distilled Buffer water ½ MD MD ½ MD ½ SE SE ½ SE ½ MD MD ½ MD ½ SE SE ½ SE Ibuprofen Characterizations of SDs by FT-IR and Differential Scanning Calorimetric (DSC) Studies % T g f e % T Fig. 1- FT-IR spectra of a) Ibuprofen, b) Poloxamer 188, c) 1 MD, d) 1 SE, e) Poloxamer 407, f) 1 MD and g) 1 SE. IR spectra of pure Ibuprofen, two carriers and their solid dispersions of 1:1 ratio prepared by both of the techniques are presented in the Fig. 1. The spectrum of pure ibuprofen revealed an intense peak for carbonyl-stretching of isopropionic acid group at around 1722 cm -1 (Fig. 1 a). From the spectra of both of the Poloxamers, a characteristic well defined peak was observed around 1110 cm -1. The spectra of all solid dispersions were found to contain these two prominent peaks of pure drug and carrier. In addition, no degradation of drug and carrier due to the high temperature during preparation was found from the IR spectra of solid dispersions made of melt dispersion technique. Furthermore, no significant differences were observed in the characteristic peaks and their positions in case of solid dispersions made of two different methods. The findings pointed toward the compatibility of the drug with the respective carriers and to the suitability of the preparation techniques in preparing solid dispersion. The DSC thermogram of Ibuprofen showed the apex of apparent endothermic peak at C; melting of the drug started at C and ended at C (Fig. 2). Similarly the melting point of Poloxamer 188 and Poloxamer 407 were observed at C and C respectively (Fig. 3 a and b). Solid dispersion ½ MD was found to have two endothermic peaks at C and C and a large peak of thermal decomposition at C (Fig. 3 c). But at the higher ratio (1:1.5), the two melting peaks merged into a single peak at C (Fig. 3 e) and a narrow peak for decomposition at higher temperature. Similar happening were found from the thermograms of SDs with Poloxamer 407 also. At 1:0.5 ratio, ½ MD exhibited two separate peaks at C and C (Fig. 3 d). Most likely the first one was of the polymer and the second one for the drug itself. At elevated temperature of C, the SD showed an endothermic peak of thermal decomposition. On addition of more carriers to the SD at 1:1.5 d c b a

5 Md. Abdullah Al Masumet al. /BioMedRx 2013,1(5), ratio, the peaks of polymer and drug combined in a single peak at a a position of C (Fig. 3 f) and the decomposition peak at elevated temperature was eliminated. Thus SDs of lower carrier ratio (1:0.5) showed two separate peaks of carrier and drug that shifted towards lower temperature and a thermal decomposition at higher temperature. SDs with greater carrier content showed no separate peaks for drug and polymer. This absence or shifting of peak position is an indication of possibilities of interaction between the drug and carrier particularly at higher temperature. Similar findings were reported by Elkordy and Essa, , and they claimed the shifting of peak was caused by the decrease of crystallinity of drug and some amorphous formation. They also postulated the enhanced dissolution rate was achieved by these changes in particle shape and sizes in the SDs. The absence of individual peak and its shifting towards lower melting position can also be explained by possibilities of formation of eutectic mixture. In a binary solid system drug and the polymer form a eutectic system if the drug is soluble in the molten polymer at the melting temperature of the polymer or vice versa. 14 Ibuprofen may be dissolved in molten Poloxamer having a lower melting point of C and formed a eutectic system that undergoes melting at a comparatively lower temperature region. Ibuprofen has been reported to form eutectics with poloxamers at around 35% w/w concentration in the mixture. 15 When the content of Poloxamer was relatively lower (at 1:0.5 ratio), some portions of Ibuprofen dissolved and hence, a little peak for the remaining drug was obtained (Fig. 3 c and d). But on addition of more carrier on the SDs (ratio 1:1.5), made the whole drug dissolved in the molten polymer and therefore the peak of drug was absent for 1½ MD and 1½ MD. The formation of eutectic system by Ibuprofen and Poloxamer at elevated temperature was also reported by Ali et al., and Sudha et al., Complete miscibility of Ibuprofen with Poloxamer in liquid phase might have some interaction at elevated temperature but there would be negligible polymer-drug interaction in the solid state. 15, 17 This was further supported by the FT-IR spectra. c b d Fig. 2- DSC thermogram of Ibuprofen.

6 Md. Abdullah Al Masumet al. /BioMedRx 2013,1(5), e F Tim e (m in.) b c P4 ½ M D P4 1 M D P4 1½ M D P4 ½ SE P4 1 SE P4 1½ SE Ibuprofen P1 ½ PM P1 1 PM P1 1½ PM P4 ½ PM P4 1 PM P4 1½ PM Ibuprofen Time (min.) d Fig. 3- DSC thermogram of a) Poloxamer 188, b) Poloxamer 407, c) ½ MD, d) ½ MD, e) 1½ MD and f) 1½ MD In Vitro Dissolution Studies In vitro drug release study of solid dispersions and physical mixtures were performed in phosphate buffer (ph 7.2) and 0.1M HCl media. Release profile of Ibuprofen from solid dispersions in phosphate buffer media (ph 7.2) showed prominent improvement of dissolution characteristics. All the prepared solid dispersions were found to release about 100% drug within 5 minutes while the pure drug dissolved only 48.27% at that time point (Fig. 4 b & d). Thus the obtained solid dispersions were found effective to improve the dissolution rate to a significant extent. SD of 1 MD and 1½ SE showed the fastest drug release rate (100.20% and % within 5 minutes) Time (min.) a P1 ½ MD P1 1 MD P1 1½ MD P1 ½ SE P1 1 SE P1 1½ SE Ibuprofen Tim e (m in.) ½ M D 1 M D Tim e (m in.) ½ M D 1 M D 1 ½ M D ½ SE 1 SE 1 ½ M D ½ SE 1 SE 1 ½ SE Ibuprofe n P1 ½ PM P1 1 PM P1 1½ PM P4 ½ PM P4 1 PM P4 1½ PM Ibuprofen Tim e (m in.) 1 ½ SE Ibuprofe n Fig. 4- In vitro release of Ibuprofen from: SD with Poloxamer 188 in acidic media (a) and buffer media (b), from SD with Poloxamer 407 in acidic media (c) and buffer media (d), and from physical mixture in acidic media (e) and buffer media (f). e d

7 In vitro drug release study was also carried out in acidic medium. In 0.1 N HCl media, pure Ibuprofen dissolved only 5.89% after 60 minutes of dissolution, whereas 1 MD released 67.56% and 1 MD went 38.21% dissolution in same time period (Fig. 4 a & c). Similar enhancement of drug release pattern was observed for SDs made of solvent evaporation technique also. 1½ SE and 1½ SE were found to release 27.69% and 44.77% drug within 1 hr. An increasing order of release pattern was observed for solid dispersions with Poloxamer 407 prepared by both techniques on increase of the carrier content in the dispersions %, 38.78% and 44.77% drug were released from the SDs made of Solvent Evaporation method having ratio of 1:0.5, 1:1 and 1:1.5 respectively (Fig. 4 c). Drug release was also improved for the physical mixtures with Poloxamer 188 and 407. Higher dissolution of drug was found from PMs containing higher amount of carrier. But the solid dispersions were found to have better rate and extent than those of physical mixtures at each ratio. For further characterization of the drug release data obtained at buffer media, MDT (mean dissolution time), T 50%, T 80% and percent dissolution efficiency (DE) were calculated. MDT value of all the solid dispersions and physical mixtures were found significantly lower than that of the drug alone. It indicated to the rapidity in drug release rate from the prepared dispersion systems. Preparation 1½ SE was found to have the lowest MDT value (0.013 minute), whereas the drug had a value of Besides, the MDT values of prepared solid dispersions were found much smaller than those of physical mixtures at the same ratio that pointed toward the efficacy of the solid dispersion technique. T 50% and T 80% values of some prepared SDs were found very close to zero that also pointed to the rapidity of drug release. From the dissolution efficiency profiles, it was observed that the dissolution efficiency of ibuprofen from all solid dispersion systems increased markedly corresponding to the pure ibuprofen. After only 5 minutes of dissolution, dissolution efficiency of the SDs with Poloxamer 188 and Poloxamer 407 were found from 40.03% to 50.11% and from 40.42% to 45.13% respectively. At the same time period, the pure drug was found to have a DE value of only 24.14% (Table 3). The Table 3- Mean dissolution time (MDT), T 50%, T 80% (in minutes ), % DE and % DE 5 values for pure ibuprofen, SDs and PMs (Medium: min 10 min Phosphate buffer ph 7.2) Name MDT T 50% T 80% % DE 5 min % DE 10 min ½ MD MD ½ MD ½ SE SE ½ SE ½ PM PM ½ PM ½ MD MD ½ MD ½ SE SE ½ SE ½ PM PM ½ PM Ibuprofen Md. Abdullah Al Masumet al. /BioMedRx 2013,1(5), enhancement was further continued to later period as suggested by the % DE value at 10 min. In all the cases, solid dispersions were found relatively higher release rate and extent than the prepared physical mixtures Characterization of prepared capsules Capsules were prepared by hand filling method and de-dusted after filling and kept in desiccators until further use. Each capsule shell was weighed before and after filling and average capsule weight was calculated and found satisfactory. In vitro disintegration time for each capsule was found within 3.2 to 5.4 minutes (Table 4). In the dissolution study, the capsules were floating initially. But on progression of time, capsules sunk and the shell was broken to release the incorporated mass. The capsules were found to release the drug in a similar fashion with that of solid dispersions. All the formulation of SD released 79.25% to 85.93% drug within 15 minutes whereas the drug alone released only 59.54% from the capsules (Fig. 5). Formulation F 1 ( 1 MD) has shown fastest release profile compared to other formulations (100.78% within only 20 minutes). Rest of the formulations released 100% drug within only 30 minutes. Table 4.-Characterization of prepared capsules Formulation Content Avg. empty Avg. capsule Disintegration No. shell weight weight (mg) time (min) (mg) F1 1 MD 95.1± ± ±0.4 F2 1 SE 95.4± ± ±0.3 F3 1 MD 95.5± ± ±0.1 F4 1 MD 94.8± ± ±0.4 F5 Ibuprofen 94.5± ± ± F1 (P1 1 MD) F2 (P1 1 SE) F3 (P4 1 MD) F4 (P4 1 SE) F5 (Ibuprofen) Time (min.) Fig. 5- In vitro release of Ibuprofen from prepared capsules In between the two carriers used in this study, Poloxamer 407 was found to improve the solubility and dissolution characteristics to a greater extent than the Poloxamer 188. It showed significant enhancement of solubility property particularly at acidic and aqueous media. Therefore, all the SDs exhibit clearly distinguishable improvement of

8 Md. Abdullah Al Masumet al. /BioMedRx 2013,1(5), dissolution in 0.1 N HCl media. It might be caused by the structural composition and higher molecular weight of Poloxamer 407. Poloxamers are nonionic polyoxyethylene-polyoxypropylene copolymers; the polyoxyethylene segment is hydrophilic while the polyoxypropylene segment is hydrophobic. 18 Greater hydrophilic and hydrophobic content of Poloxamer 407 might be responsible for the better emulsifying property which in turn demonstrates higher solubility followed by better dissolution. Solid dispersion technique has once again proved its efficacy to improve solubility characteristics and dissolution properties corresponding to the physical mixtures. Incorporation a of soluble carrier in between insoluble drug at molecular level offered by the solid dispersion technique is the key to the success of the preparations. Both the melt dispersion and the solvent evaporation technique were found effective for Ibuprofen to improve its solubility parameter. The binary solid dispersion of Ibuprofen with Poloxamer 188 made by melt dispersion technique ( 1 MD) was found the best preparation among the solid dispersions and physical mixtures due to having greater solubility at each three media and better dissolution at two media. 4.Conclusion Solid dispersions of practically water insoluble Ibuprofen were prepared by using two grades of Poloxamer by melt dispersion and solvent evaporation technique at three different ratios. The compatibility between the drug and carrier and the suitability of solid dispersion technique were evaluated by FT-IR and DSE thermal study. Improvement in the solubility characteristics of SDs were compared by saturated solubility analysis in three medium. Drug release study was carried out in two different dissolution media and compared to the physical mixtures. Data obtained from the studies showed remarkable improvement of the release property of Ibuprofen from the solid dispersions. ACKNOWLEDGEMENT The authors would like to express their gratitude to Dr. Mala Khan for DSC analysis at Bangladesh Council of Scientific and Industrial Research (BCSIR). Source of support: Nil, Conflict of interest: None Declared REFERENCES 1. Tripathi KD. Non steroidal anti inflammatory drugs and anti pyretic analgesics, Essentials of medical pharmacology. 5 th ed. Jaypee Brothers: New Delhi; p USP 32-NF 27. The United States pharmacopeia The National Formulary. Rockville, MD: The United States Pharmacopeial Convention, Inc Herzfeld CD, Kummel R. Dissociation constant, solubilities and dissolution rate of some selective non steroidal anti inflammatory drugs. Drug Dev Ind Pharm. 1983; 9(5): Aparna K, Meenakshi B, Monika S. Improvement of dissolution rate and solubility of nifedipine by formulation of solid dispersions. The Pharma Res J. 2010; 4: Datta A, Ghosh NS, Ghosh S, Debnath S, Kumar S, Bhattacharjee C, Chandu AN. Development, characterization and solubility study of solid dispersion of nifedipine by solvent evaporation method using ß-cyclodextrin. J Adv Pharm Res. 2011; 2: Satinder A, Stephen S. Handbook of Modern Pharmaceutical Analysis. 3 rd ed. Academic Press: San Diego USA and London UK; p Carter SJ. Cooper and Gunn s Tutorial Pharmacy. 6 th ed. CBS Publishers and Distribotors: New Delhi; p Dabbagh MA, Taghipour B. Investigation of Solid Dispersion Technique in Improvement of Physicochemical Characteristics of Ibuprofen Powder. Iranian J Pharm Sci. 2007; 3: Ramakrishna GS, Reddy KA, Reddy BJ, Dinakar P, Rao PR, Bhavanam PR. Enhanced dissolution rate of ibuprofen by solid dispersion method. J Inn trends Pharm Sci. 2010; 1(4): Islam MS, Mehjabeen K, Mustary I, Khan F, Jalil R. Improvement of dissolution of Ibuprofen and Fenofibrate by Poloxamer based solid dispersion. Bangladesh Pharm J. 2010; 13: Giri TK, Badwaik H, Alexander A, Tripathi DK. Solubility enhancement of ibuprofen in the presence of hydrophilic polymer and surfactant. Int J App Bio Pharm Tech. 2010; 1: Masum MAA, Sharmin F, Islam SMA, Reza MS. Enhancement of Solubility and Dissolution Characteristics of Ibuprofen by Solid Dispersion Technique. Dhaka Univ J Pharm Sci. 2012; 11(1): Elkordy AA, Essa EA. Effects of Spray Drying and Spray Chilling on Ibuprofen Dissolution. Iranian J Pharm Sci. 2010; 6(1): Sudha RV, Zeren W, Stefanie H, Steven LK. Factors affecting the formation of eutectic solid dispersions and their dissolution behavior. J Pharm Sci. 2007; 96: Passerini N, G-Rodriguez ML, Cavallari C, Rodriguez L, Albertini B. Preparation and characterization of ibuprofenpoloxamer 188 granules obtained by melt granulation. Eur J Pharm Sci. 2002; 15: Ali WW, Williams AC, Rawlinson CF. Stochiometrically governed molecular interactions in drug: Poloxamer solid dispersions. Int J Pharm. 2010; 391(1-2): Newa M, Bhandari KH, Oh DH, Kim YR, Sung JH, Kim JO, Woo JS, Choi HG, Yong CS. Enhanced Dissolution of Ibuprofen Using Solid Dispersion with Poloxamer 407. Arch Pharm Res. 2008; 31(11): Rowe RC, Sheskey PJ, Owen SC. Handbook of pharmaceutical excipients. 5 th ed. Pharmaceutical Press & the American Pharmacists Association: London; p