Bioavailability Of Ibuprofen Research Articles

BIOAVAILABILITAS TABLET IBUPROFEN PADA PEMBERIAN BERSAMAAN DENGAN EKSTRAK AIR HERBA PEGAGAN (Centella asiatica (L) Urban) PADA KELINCI JANTAN

The tendency to use herbal drug simultaneously with synthetic drug may result in an interaction. Based on research, aqueous extract of Centella asiatica (L) Urban contains saponin (asiaticoside and madecassoside) compounds that inhibit CYP450 and is a safe herbal alternative that is used for anti-inflammatory treatment. The aim of this study was to investigate the effect of aqueous extract of Centella asiatica (L) Urban to the ibuprofen tablet bioavailability in male rabbits. Both compounds are metabolized by CYP450 enzymes in the same way with different mechanism. The cross over design with the same subject was used in this study. The samples consisted of 400 mg ibuprofen with 0%b/v, 25%b/v, 50%b/v dan 100%b/v aqueous extract of Centella asiatica (L) Urban respectively. The blood were taken after 0; 0,5; 1; 1,5; 2; 2,5; 3; 3,5; 4; 6; 8; 10 hours after samples treatment, then the ibuprofen plasma concentration were determined spectrophotometrically. The results then were used to evaluat the bioavailability parameters: tmaks, Cpmaks, and AUC and were analyzed using ANOVA test in the same way as well as the 95% trust standart. The results showed, the use of ibuprofen tablet stimultaneously with aqueous extract of Centella asiatica (L) Urban increased Cpmaks dan AUC, but there were no influence to the tmaks value. The use of ibuprofen tablet stimultaneously with 50 %b/v and 100 %b/v aqueous extract of Centella asiatica (L) Urban had a significant influence to the bioavailability of ibuprofen.

Development of novel ibuprofen-loaded solid dispersion with enhanced bioavailability using cycloamylose

To develop a novel ibuprofen-loaded solid dispersion with enhanced bioavailability using cycloamylose, it was prepared using spray-drying techniques with cycloamylose at a weight ratio of 1:1. The effect of cycloamylose on aqueous solubility of ibuprofen was investigated. The physicochemical properties of solid dispersions were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction. The dissolution and bioavailability in rats were evaluated compared with ibuprofen powder. This ibuprofen-loaded solid dispersion improved about 14-fold drug solubility. Ibuprofen was present in an unchanged crystalline state, and cycloamylose played the simple role of a solubilizing agent in this solid dispersion. Moreover, the dispersion gave 2-fold higher AUC (area under the drug concentration-time curve) value compared with a ibuprofen powder, indicating that it improved the oral bioavailability of ibuprofen in rats. Thus, the solid dispersion may be useful to deliver ibuprofen with enhanced bioavailability without crystalline change.

Ibuprofen–phospholipid solid dispersions: Improved dissolution and gastric tolerance

Solid dispersions of ibuprofen with various phospholipids were prepared, and the effect of phospholipids on the in vitro dissolution and in vivo gastrointestinal toxicity of ibuprofen was evaluated. Most phospholipids improved the dissolution of ibuprofen; dimyristoylphosphatidyl-glycerol (DMPG) had the greatest effect. At 45 min, the extent of dissolution of ibuprofen from the ibuprofen–DMPG system (weight ratio 9:1) increased about 69% compared to ibuprofen alone; the initial rate of dissolution increased sevenfold. Increasing the DMPG content from 9:1 to 4:1 in this system did not significantly increase the rate and the extent of dissolution. X-ray diffraction and scanning electron micrograph indicated a smaller crystallite size of ibuprofen with fairly uniform distribution in the ibuprofen–DMPG solid dispersion. A small amount of carrier phospholipid significantly increases the rate and the extent of dissolution, which may increase the bioavailability of ibuprofen. The number of ulcers >0.5 mm in size formed in the gastric mucosa of rats following ibuprofen, DMPG, DMPC and DPPC solid dispersions (ibuprofen and phospholipid weight ratio 4:1) were 8.6 ± 6.2, 3.9 ± 5.3, 5.3 ± 4.9 and 9.1 ± 7.4, respectively. Solid dispersion of ibuprofen with DMPG was significantly less irritating to the gastric mucosa than ibuprofen itself (one-way ANOVA, p < 0.05). Solid dispersion of ibuprofen and DMPG decreases the gastric side effects of ibuprofen.

Preparation and evaluation of ibuprofen-loaded microemulsion for improvement of oral bioavailability

The purpose of the current study was to improve the solubility of ibuprofen, a poorly water-soluble drug, in a microemulsion system that is suitable for oral administration. Microemulsion was prepared using different sorts of oils, surfactants, and co-surfactants. Pseudo-ternary phase diagrams were used to evaluate the microemulsion domain. The formulations were characterized by solubility of the drug in the vehicle, droplet size, and drug release. The optimal formulation consists of 17% Labrafil M 1944CS, 28% Cremophor RH40/Transcutol P (3:1, w/w), and 55% water, with a maximum solubility of ibuprofen up to 60.3 mg/ml. The mean droplet size of microemulsion was 57 nm. The pharmacokinetic study of microemulsion was performed in rats and compared with granule formulation. The microemulsion has significantly increased the Cmax and area under the curve (AUC) compared to that of the granule (p < 0.05). The relative bioavailability of ibuprofen in microemulsions was 1.9-fold higher than that of the granule. These results indicated that this novel microemulsion is a useful formulation for enhancing the oral bioavailability of ibuprofen.

Ibuprofen–arginine generates nitric oxide and has enhanced anti-inflammatory effects

Ibuprofen, a chiral non-steroidal anti-inflammatory drug chemically related to fenoprofen and naproxen, has moderate but definite anti-inflammatory, analgesic and antipyretic properties, with considerably less gastrointestinal adverse effect than other drugs in the same family. Currently available in the market are preparations in which bioavailability of ibuprofen is increased by salification with various salts. We have investigated the pharmacological properties of one such salt, ibuprofen–arginine, of biological interest because l-arginine acts as substrate of the nitric oxide (NO) synthesising enzymes. Using epithelial HeLa cells expressing the endothelial NO synthase we show that ibuprofen–arginine releases NO and that this NO protects against the cytotoxic apoptogenic effects of staurosporine. We also found that ibuprofen–arginine is endowed with enhanced anti-inflammatory effects with respect to ibuprofen, as shown by reduced hind paw oedema, neutrophil infiltration and chondrocyte apoptosis in collagen-induced mouse arthritis, a model of chronic inflammation. NO has pleiotropic beneficial effects that may contribute to limit inflammation and anti-inflammatory compounds able to release NO display higher efficacy than the parent drugs in defined clinical settings. Our results open the possibility that NO generation contributes to the enhanced anti-inflammatory effects of ibuprofen–arginine vs. ibuprofen, suggesting co-administration of anti-inflammatory drugs and arginine as an additional way to exploit the beneficial effects of NO.

Clinical trial: comparison of ibuprofen‐phosphatidylcholine and ibuprofen on the gastrointestinal safety and analgesic efficacy in osteoarthritic patients

Chronic use of NSAIDs is associated with gastrointestinal (GI) toxicity that increases with age. To evaluate the GI safety and therapeutic efficacy of ibuprofen chemically associated with phosphatidylcholine (PC) in osteoarthritic (OA) patients. A randomized, double-blind trial of 125 patients was performed. A dose of 2400 mg/day of ibuprofen or an equivalent dose of ibuprofen-PC was administered for 6 weeks. GI safety was assessed by endoscopy. Efficacy was assessed by scores of analgesia and anti-inflammatory activity. Bioavailability of ibuprofen was pharmacokinetically assessed. Ibuprofen-PC and ibuprofen provided similar bioavailability/therapeutic efficacy. In the evaluable subjects, a trend for improved GI safety in the ibuprofen-PC group compared with ibuprofen that did not reach statistical significance was observed. However, in patients aged >55 years, a statistically significant advantage for ibuprofen-PC treatment vs. ibuprofen in the prevention of NSAID-induced gut injury was observed with increases in both mean Lanza scores and the risk of developing >2 erosions or an ulcer. Ibuprofen-PC was well tolerated with no major adverse events observed. Ibuprofen-PC is an effective osteoarthritic agent with an improved GI safety profile compared with ibuprofen in older OA patients, who are most susceptible to NSAID-induced gastroduodenal injury.

Enhancement of Solubility, Dissolution and Bioavailability of Ibuprofen in Solid Dispersion Systems

To improve its solubility, dissolution, and bioavailability; Ibuprofen-polyethylene glycol 8000 (PEG 8000) solid dispersions (SDs) with different drug loadings were prepared, characterized by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC), and evaluated for solubility, in-vitro release, and oral bioavailability of ibuprofen in rats. Loss of individual surface properties during melting and solidification as revealed by SEM micrographs indicated the formation of effective SDs. Absence or shifting towards the lower melting temperature of the drug peak in SDs and physical mixtures in DSC study indicated the possibilities of drug-polymer interactions. Quicker release of ibuprofen from SDs in rat intestine resulted in a significant increase in AUC and C(max), and a significant decrease in T(max) over pure ibuprofen. Preliminary results of this study suggested that the preparation of ibuprofen SDs using PEG 8000 as a meltable hydrophilic polymer carrier could be a promising approach to improve solubility, dissolution and bioavailability of ibuprofen.

Preparation and Evaluation of Immediate Release Ibuprofen Solid Dispersions Using Polyethylene Glycol 4000

To improve its dissolution, ibuprofen solid dispersions (SDs) were prepared in a relatively easy and simple manner, characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR), and evaluated for solubility, in-vitro drug release and oral bioavailability of ibuprofen in rats. Loss of individual surface properties during melting and resolidification as revealed by SEM micrographs indicated the formation of effective SDs. Absence or shifting towards the lower melting temperature of the drug peak in SDs and physical mixtures in DSC study indicated the possibilities of drug-polymer interactions. FT-IR spectra showed the presence of drug crystalline in SDs. Quicker release of ibuprofen from SDs in rat intestine resulted in a significant increase in AUC and Cmax, and a significant decrease in Tmax over pure ibuprofen. Preliminary results from this study suggested that the preparation of fast dissolving ibuprofen SDs by low temperature melting method using polyethylene glycol 4000 (PEG 4000) as a meltable hydrophilic polymer carrier could be a promising approach to improve solubility, dissolution and absorption rate of ibuprofen.

Preparation and Evaluation of Fast Dissolving Ibuprofen-Polyethylene Glycol 6000 Solid Dispersions

To improve its oral absorption, rapidly dissolving ibuprofen solid dispersions (SD) were prepared in a relatively easy, simple, quick, inexpensive, and reproducible manner, characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR). They were evaluated for solubility, in vitro release, and oral bioavailability of ibuprofen in rats. Loss of individual surface properties during melting and resolidification as revealed by SEM indicated the formation of effective SDs. Absence or shifting toward the lower melting temperature of the drug peak in SDs and physical mixtures in DSC study indicated the possibilities of drug-polymer interactions. However, no such interactions in the solid state were confirmed by FTIR spectra that showed the presence of drug crystalline in SDs. Quicker release of ibuprofen from SDs in rat intestine resulted in a significant increase in AUC and Cmax, and a significant decrease in Tmax over pure ibuprofen. Preliminary results from this study suggested that the preparation of fast-dissolving ibuprofen SDs by low temperature melting method using PEG 6000 as a meltable hydrophilic polymer carrier could be a promising approach to improve solubility, dissolution, and absorption rate of ibuprofen.

Novel gelatin microcapsule with bioavailability enhancement of ibuprofen using spray-drying technique

A poorly water-soluble ibuprofen and ethanol can be encapsulated in gelatin microcapsule by spray-drying technique. To develop a novel ibuprofen-loaded gelatin microcapsule with bioavailability enhancement, the effect of spray-drying conditions, gelatin, ibuprofen and sodium lauryl sulfate on the ibuprofen solubility and the amount of ethanol encapsulated in gelatin microcapsule were investigated. The ibuprofen solubility and amount of encapsulated ethanol increased as inlet temperature and amount of sodium lauryl sulfate increased, reached maximum at 105 °C and 0.6%, respectively and after that followed a rapid decrease. Furthermore, they abruptly increased as the amount of gelatin increased, reaching maximum at 4% then remaining almost stable, but the encapsulated ethanol content decreased noticeably. Likewise, the ibuprofen solubility increased as the amount of ibuprofen increased, reaching maximum at 0.5% and beyond that, there was no change in the solubility. However, the encapsulated ethanol content hardly changed irrespective of the amount of ibuprofen. Furthermore, the formula of ibuprofen-loaded gelatin microcapsule at the ratio of gelatin/ibuprofen/sodium lauryl sulfate/water/ethanol of 4/0.5/0.6/30/70 showed ibuprofen solubility of about 290 μg/ml and ethanol content of about 160 μg/mg. This gelatin microcapsule dramatically increased the initial dissolution rate of ibuprofen compared to ibuprofen powder in pH 1.2 simulated gastric fluid. Moreover, it gave significantly higher initial plasma concentrations, C max and AUC of ibuprofen in rats than did ibuprofen powder, indicating that the drug from gelatin microcapsule could be more orally absorbed in rats. Our results suggested that the enhanced oral bioavailability of ibuprofen in the gelatin microcapsule was contributed by the marked increase in the absorption rate of ibuprofen due to the crystallinity change to amorphous form and increase in dissolution rate of ibuprofen in the gelatin microcapsule in rats. Thus, the ibuprofen-loaded gelatin microcapsule developed using spray-drying technique with gelatin would be useful to deliver ibuprofen in a pattern that allows fast absorption in the initial phase, leading to better absorption.

Preparation, characterization and in vivo evaluation of ibuprofen binary solid dispersions with poloxamer 188

Ibuprofen–Poloxamer 188 (P 188) binary solid dispersions (SD) with different drug loadings were prepared, characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), and evaluated for solubility, in vitro release, and oral bioavailability of ibuprofen in rats. Loss of their individual surface properties during melting and solidification as revealed by SEM micrographs indicated the formation of effective SDs. Absence or shifting towards the lower melting temperature of the drug peak in SDs and physical mixtures in DSC study indicated the possibilities of its interactions with P 188. However, no such interactions in the solid state were confirmed by FTIR spectra which showed the presence of drug crystalline in SDs. Immediate and complete release of ibuprofen from SDs might be because of the reduction in the drug crystalline due to eutectic formation, and their dosing to fasted rats resulted in a significant increase in the area under curve (AUC) of the plasma concentration versus time curve and the maximum plasma concentration ( C max), and a significant decrease in the time to reach C max ( T max) over ibuprofen and physical mixtures.

Enhanced Oral Bioavailability of Ibuprofen in Rats by Poloxamer Gel Using Poloxamer 188 and Menthol

To improve the oral bioavailability of poorly water-soluble ibuprofen with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. The dissolution and pharmacokinetic study of ibuprofen delivered by the ibuprofen-loaded preparations composed of poloxamer 188 and menthol were then performed. In the absence of poloxamer, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that four parts menthol formed eutectic mixture with six parts ibuprofen. In the presence of poloxamer, the solutions with the same ratio of menthol to ibuprofen showed an abrupt increase in the solubility of ibuprofen. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2 mg/mL. The simultaneous addition of menthol and poloxamer 188 significantly improved the dissolution rates of ibuprofen from aqueous solution due to the ibuprofen solubility-improving effect of menthol in the presence of poloxamer. Furthermore, the ibuprofen-loaded preparation with menthol and poloxamer 188 gave significantly higher initial plasma concentrations, Cmax, and AUC of ibuprofen than did the preparation without menthol and poloxamer 188, indicating that the simultaneous addition of menthol and poloxamer 188 could improve the oral bioavailability of ibuprofen in rats. In modern pain management it is always desirable for the ibuprofen-loaded preparation with poloxamer 188 and menthol to show a rapid onset of action with a minimal phase of lag time to feel the decreased pain. From an industry point of view, it is more desirable for a formulation to be fast acting, easy to use, and cost effective. Thus, the ibuprofen-loaded preparation with poloxamer 188 and menthol was a more effective oral dosage form for poorly water-soluble ibuprofen.

Preparation of ibuprofen-loaded liquid suppository using eutectic mixture system with menthol

To prepare an ibuprofen-loaded liquid suppository using eutectic mixture with menthol, the effects of menthol and poloxamer 188 (P 188) on the aqueous solubility of ibuprofen were investigated. The physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of ibuprofen, menthol and P 188 were investigated. Then, the pharmacokinetic study of ibuprofen delivered by the liquid suppositories composed of P 188 and menthol were then performed. In the absence of P 188, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that four parts of ibuprofen formed eutectic mixture with six parts of menthol. In the presence of P 188, the solutions with the same ratio showed abrupt increase in the solubility of ibuprofen. Furthermore, the solution with ratio of 4:6 showed more than 2.5- and 6-fold increase in the solubility of ibuprofen compared with that without additives and that without menthol, respectively. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2mg/ml. Ibuprofen increased the gelation temperature and weakened the gel strength and bioadhesive force of liquid suppositories. However, menthol did the opposite due to forming the eutectic mixture with ibuprofen. The ibuprofen-loaded liquid suppository [P 188/menthol/ibuprofen (15/0.25/2.5%)] with the maximum ibuprofen solubility of 1.2mg/ml was administered easily to the anus and to remain at the administered site without leakage after the dose. Furthermore, it gave significantly higher initial plasma concentrations, Cmax and AUC of ibuprofen than did solid suppository, indicating that the drug from poloxamer gel could be more absorbed than that from solid one in rats. Thus, the liquid suppository system with P 188 and menthol, a more convenient and effective rectal dosage form for ibuprofen will be expected to enhance the rectal bioavailability of ibuprofen.

Bioavailability of ibuprofen from hot-melt extruded mini-matrices

The bioavailability of ibuprofen from hot-melt extruded mini-matrices based on ethyl cellulose and a hydrophilic excipient was tested. During the in vivo evaluation an oral dose of 300 mg ibuprofen was administered to healthy volunteers ( n=9) in a randomized cross-over study and compared with a commercially available sustained release product (Ibu-slow ®). The plasma samples were analysed by a validated HPLC-UV method. One mini-matrix formulation (F-1) consisted of 30% ibuprofen, 35% ethyl cellulose and 35% hydroxypropyl methylcellulose (Metolose ® 60 SH 50), while the second formulation (F-2) contained 60% ibuprofen, 20% ethyl cellulose and 20% xanthan gum. These mini-matrices were administered in hard gelatine capsules. Both formulations behaved in vivo as sustained release formulations with an HVD t 50% C max value (time span during which the plasma concentration is at least 50% of the C max value) of 7.6 and 12.0 h for formulations F-1 and F-2, respectively, whereas a value of 5.2 h was obtained for Ibu-slow ®. Although a significantly higher C max and AUC 0–24 h was seen for the reference product, the relative bioavailability of both experimental formulations was about 80%.

Effect of Tamarindus indica. L on the bioavailability of ibuprofen in healthy human volunteers.

The influence of Tamarindus indica L fruit extract incorporated in a traditional meal on the bioavailability of Ibuprofen tablets 400 mg dose when given concurrently was studied in 6 healthy human volunteers. There was a statistically significant increase in the plasma levels of Ibuprofen and its metabolites hydroxy-ibuprofen and carboxy-ibuprofen respectively, when the meal containing Tamarindus indica fruit extract was administered with the ibuprofen tablets than when taken under fasting state or with the meal without the fruit extract. The C(max), AUC(0-6 hr) and Ka for ibuprofen increased from 38 +/- 0.70 microg/ml to 42 +/- 0.98 microg/ml (p > 0.05); and 28.03 +/- 2.40 microg/ml x hr to 56.51 +/- 0.16 microg/ml x hr (p < 0.05) and 1.048 +/- 0.02hr(-1) to 2.781 +/- 0.11 hr(-1) (p < 0.05) respectively. There was no change in the t(max) (120.00 +/- 0.43m) but there was a decrease in the k(el) from 0.63 +/- 0.20 hr(-1) to 0.46 +/- 0.11 hr(-1) (p<0.05). Similarly the C(max), AUC(0-6 h) and Ka for hydroxy-ibuprofen rose from 43 +/- 0.76 microg/ml to 45 +/- 0.16 microg/ml (p < 0.05); 39.04 +/- 2.30 microg/ml x hr to 59.49 +/- 2.39 microg/ml.hr in (p < 0.05) and 1.498 +/- 0.79hr(-1) to 3.442 +/- 0.23 hr(-1) (p < 0.05) respectively; while the C(max), AUC(0-6 h) and Ka for carboxy-ibuprofen rose from 48 +/- 0.7 microg/ml to 51 +/- 0.16 microg/ml (p < 0.05); 41.972 +/- 0.68 microg/ml x hr to 63.948 +/- 0.12 microg/ml x hr (p < 0.05) and 1.649 +/- 0.08 hr(-1) to 4.187 +/- 0.42 hr(-1) (p < 0.05) respectively. The study has indicated that Tamarindus indica L. fruit extract significantly increased the bioavailability of Ibuprofen.

Enhanced Bioavailability of Process-Induced Fast-Dissolving Ibuprofen Cogranulated with β-Cyclodextrin

The objectives of this study were to evaluate the bioavailability of cogranulated and oven-dried ibuprofen (IBU) and beta-cyclodextrin (betaCD), in comparison to a physical mixture, and to examine the effect of endogenous bile on the bioavailability of the drug. In vitro dissolution studies were performed using USP type 2 apparatus. The granules and physical mixture were administered perorally in a crossover fashion, to male Wistar bile duct-nonligated rats. The granules were also perorally administered to bile duct-ligated rats. Blood samples were taken at different time intervals and the plasma analyzed for IBU. Dissolution of granules was faster than the physical mixture due to faster IBU-betaCD complex formation in solution from the former than the latter. The in vivo study showed that C(max), AUC(0-8), and the absolute bioavailability for the granules (49.0 microg/mL, 57.0 h x microg/mL and 80.6%, respectively) were almost one and half times that of the physical mixture (32.2 microg/mL, 38.4 h x microg/mL and 53.1%, respectively). However, in bile duct-ligated rats, lower C(max) and AUC(0-8) (15.9 microg/mL and 14.4 h x microg/mL, respectively) were obtained for the granules. Phase solubility study of IBU in an aqueous betaCD solution in the presence of the bile salt (sodium cholate), showed an increase in the solubility of IBU. Moreover, the stability constant value for the IBU-betaCD complex was also found to decrease as the sodium cholate concentration increased. These results indicated that the enhancement in the bioavailability of IBU was due to faster in-solution complex formation, and micelllar solubilization by the bile salt.

Effect of sodium/potassium salt (potash) on the bioavailability of ibuprofen in healthy human volunteers.

The influence of sodium/potassium salt water extract incorporated in a traditional meal on the bioavailability of Ibuprofen tablets 400mg dose was studied in 6 healthy human volunteers. There was a statistically significant decrease in the plasma levels of ibuprofen, and its metabolites, hydroxy-ibuprofen and carboxy-ibuprofen, respectively, when the meal containing sodium/potassium salt extract was administered with the ibuprofen tablets than when taken under fasting state or with the meal without the fruit extract. The Cmax, AUC0-6hr and Ka for ibuprofen decreased from 38.04 +/- 0.70microg/ml to 20.06 +/- 1.21microg/ml (p<0.05); 28.030 +/- 2.40microg/ml.hr to 14.180 +/- 1.12microg/ml.hr (p<0.05) and 1.048 +/- 0.02hr(-1) to 0.602 +/- 0.03hr(-1). Similarly, the Cmax for hydroxy-ibuprofen and carboxy-ibuprofen decreases from 43.04 +/- 0.76microg/ml to 27.21 +/- 0.24microg/ml (p<0.05) and 48 +/- 0.71microg/ml to 31.08 +/- 0.12microg/ml (p<0.05) respectively; while AUC0-6hr for hydroxy-ibuprofen decreased from 34.120 +/- 0.49microg/ml.hr to 16.410 +/- 0.27microg/ml.hr while that of carboxy-ibuprofen decreased from 36.121 +/- 1.97microg/ml.hr to 19.278 +/- 0.92microg/ml.hr respectively. The Kel for hydroxy-ibuprofen increased from 0.71 +/- 0.94 hr(-1) to 0.81 +/- 0.21 hr(-1) (p<0.05) respectively. The study has indicated that sodium/potassium salt extract significantly decreased the bioavailability of ibuprofen.

Percutaneous absorption of non-steroidal anti-inflammatory drugs from in situ gelling xyloglucan formulations in rats

The potential of gels formed in situ by dilute aqueous solutions of a xyloglucan polysaccharide derived from tamarind seed as sustained release vehicles for percutaneous administration of non-steroidal anti-inflammatory drugs has been assessed by in vitro and in vivo studies. Chilled aqueous solutions of xyloglucan that had been partially degraded by β-galactosidase formed gels at concentrations of 1–2% w/w when warmed to 37 °C. The in vitro release of ibuprofen and ketoprofen at pH 7.4 from the enzyme degraded xyloglucan gels and the subsequent permeation of these fully ionized drugs through cellulose membranes followed root-time kinetics over a period of 12 h after an initial lag period. Diffusion coefficients were appreciably higher when the drugs were released from 1.5% w/w xyloglucan gels than when released from 25% w/w Pluronic F127 gels formed in situ under identical conditions. The difference in release rates was attributed to differences in the structure of the gels. The permeation rate of ibuprofen through excised skin was higher than that of ketoprofen when released from both gels, but of similar magnitude through cellulose membranes. Plasma concentrations of ibuprofen and ketoprofen from gels formed in situ following topical application of chilled aqueous solutions of xyloglucan and Pluronic F127 to the abdominal skin of rats were compared. The bioavailabilities of ibuprofen and ketoprofen were significantly higher when released from xyloglucan gels compared to Pluronic F127 gels. Occlusive dressing techniques had a greater enhancing effect on the bioavailability of ibuprofen when released from Pluronic gels.

자가유화 약물전달시스템을 이용한 이부프로펜의 용출개선 및 흰쥐에서의 생체이용률 평가

A self-microemulsifying drug delivery system(SMEDDS) composed of Cremophor , and Lauroglycol was prepared for the enhancement of solubility, dissolution rate and bioavailability of ibuprofen(IBP), which is water-insoluble but soluble in oils and surfactants. Phase diagram with various regions including microemulsion area was depicted. The SMEDDS was encapsulated in soft gelatin capsules and their dissolution characteristics in various media were observed in comparison to the generic products commercially available in the market. Soft capsules of SMEDDS formulation showed better dissolution profiles, especially in acidic condition, than the others. For the period of 1 hr dissolution in pH 1.2 medium, it reached over 70% dissolution from soft capsules, compared to less than 40% dissolution from commercial reference tablets. On the other hand, in vivo pharmacokinetic parameters were obtained after oral administrations of different IBP preparations to Sprague Dawley rats. SMEDDS formulation showed higher and greater than the suspension of reference tablet or IBP powder. Therefore, it is possible to conclude that a newly developed soft capsules employing SMEDDS provides an alternative preparation to improve oral bioavailability of IBP.

Pharmacokinetic Study of a New Ibuprofen 600mg plus Codeine 30mg Combination versus Ibuprofen or Codeine Alone in Single Oral Doses in Healthy Volunteers

Objective: To compare the bioavailability parameter values of ibuprofen 600mg or codeine 30mg when administered in a new combined solid oral formulation versus each agent administered alone. Design: Non-blind, comparative, crossover, three-way (ibuprofen, codeine, ibuprofen plus codeine) randomised clinical trial. Setting: Phase 1 study unit. Subjects: 24 healthy volunteers of both genders (12 males and 12 females) with the following average characteristics: age 22.6 years; bodyweight 63.2kg; height 171cm; body mass index 21.47 kg/m2. Interventions: During each study period, a single oral dose of one of the formulations was administered, and 13 plasma samples were obtained to determine drug concentrations and calculate pharamcokinetic parameter values. Results: The pharmacokinetic parameter values [mean ± standard deviation, except median for time to maximum plasma concentration (tmax)] calculated for each drug and formulation were as follows: For ibuprofen (combined with codeine) versus ibuprofen alone: area under the concentration-time curve from time zero to infinity (AUC0-∞), 202.06 ± 43.62 vs 204.19 ± 52.79 mg·h/L; maximum plasma concentration (Cmax), 64.93 ± 11.91 vs 57.01 ± 15.47 mg/L; tmax, 1.00 vs 1.50h. The 90% confidence intervals (CI90) of the ratios (%) of logarithmically transformed values were: AUC0-∞ 95.88 to 104.22; Cmax 104.75 to 129.63; the CI90 (Wilcoxon test) of the median difference in tmax was −0.80 to −0.13h. For codeine (combined with ibuprofen) versus codeine alone: AUC0-∞ 417.82 ±115.55 vs 354.36 ±114.43 μg·h/L; Cmax115.12 ± 38.85 vs 89.05 ± 27.09 μg/L; tmax 1.00 vs 1.00h. The CI90 of the ratios (%) of logarithmically transformed values were: AUC0-∞ 111.84 to 126.18; Cmax 116.66 to 139.57; the CI90 (Wilcoxon test) of the median difference in tmax was −0.25 to 0.17h. Conclusions: The rate and extent of ibuprofen release/absorption from both formulations are within bioequivalence limits. The extent of absorption of codeine is slightly greater from the combination form, with a similar rate of release/absorption. The slight differences found are attributable to the galenic formulations. These results confirm the good bioavailability of ibuprofen and codeine from the new formulation, and exclude any impairment of absorption when the drugs are formulated in combination.