Effects of lipid formulations on clove extract spray dried powders: comparison of physicochemical properties,storage stability and in vitro intestinal permeation

Abstract

Clove is an aromatic plant spice with potent antioxidant and anti-inflammatory activity. Eugenol is the main compound which contributes to such medicinal and nutritional benefits. To date, the formulation of unstable, volatile and poorly water-soluble compounds remains a challenging task. Lipid formulations can be used to improve physicochemical and biopharmaceutical properties of poorly soluble compounds. The aim of this study is to investigate the effects of lipids, such as Gelucire and Compritol on physicochemical properties; stability and in vitro intestinal permeation of spray dried powdered formulations loaded with clove’s bioactive compounds. Results showed that eugenol retention in spray-dried powders could be correlated with antioxidant activity and with mass recovery after spray drying. Adding Gelucire but not Compritol to clove extract formulations, improved solubility of spray dried powders. Stability test in high humidity environment (63.5% RH) suggested that formulations including both Gelucire and Compritol were significantly more stable compared to the formulation without any lipid at the two tested temperatures (25?°C and 40?°C). This suggests that lipid additions to clove (Syzygium aromaticum) extract formulations provide protective effects for the spray dried powders in high-humidity environments. In addition, results from in vitro intestinal permeation studies suggested that eugenol uptake, was not being hindered by transporters nor was the absorption being affected by lipid formulations.     

Lornoxicam,a new potent NSAID with an improved tolerability profile

Lornoxicam is a member of the oxicam group of nonsteroidal antiinflammatory drugs (NSAIDs). Oxicams have potent antiinflammatory and analgesic effects, but their use is associated with a high risk of gastrointestinal adverse effects. Lornoxicam has been shown to be at least as effective as comparative NSAIDs and more effective than 10 mg morphine when used at doses > or = 8 mg to control pain after oral surgery. In addition, oral doses of lornoxicam of 16-24 mg daily have been more effective than tramadol 300 mg daily in pain following knee surgery. Lornoxicam combines the high therapeutic potency of oxicams with an improved gastrointestinal toxicity profile as compared to naproxen, for example. This is probably due to the short half-life of lornoxicam as compared to the other oxicams. The clinical trials published so far, mostly comparative, clearly do- cument the efficacy of lornoxicam as a potent analgesic with excellent antiinflammatory properties in a range of painful and/or inflammatory conditions, including postoperative pain and rheumatoid arthritis.     

氯诺昔康用于术后患者自控镇痛的临床疗效和安全性

目的:评价非甾体抗炎药氯诺昔康用于妇科全子宫切除术后患者自控镇痛(PCA)的疗效及安全性。方法:60例全身麻醉下行全子宫切除术术后出现中度以上疼痛的患者随机分为氯诺昔康组和吗啡组。患者根据需要启动PCA泵(氯诺昔康0.8mg/次,吗啡1mg/次,锁定时间5min)。由疼痛缓解程度(PAR)、疼痛缓解总和(TOT-PAR)和患者24h镇痛总体效果来评价镇痛效果,同时监测血小板聚集率、肝、肾功能,并观察胃肠道反应等。结果:氯诺昔康组和吗啡组的TOTPAR和镇痛总体印象评分无显著性差异(P>0.05)。吗啡组起效早于氯诺昔康 组。氯诺昔康组的恶心呕吐的发生率明显低于吗啡组。2组血小板聚集率无显著性差异(P>0.05)。结论:氯诺昔康用于妇科全子宫切除术后PCA镇痛,其镇痛效应与吗啡相近,不良反应较少。     

Gastrointestinal tolerability of lornoxicam compared to that of naproxen in healthy male volunteers

Background and Aim: Gastrointestinal effects are common adverse effects associated with nonsteroidal anti-inflammatory drugs (NSAIDs). Lornoxicam is a new nonsteroidal anti-inflammatory drug and its gastroduodenal tolerability was compared to that of naproxen in a randomized, double-blind, crossover study.
Methods: Eighteen healthy male volunteers received lornoxicam 8 mg b.d. or naproxen 500 mg b.d. administered orally over two 7-day dosing periods. Upper endoscopy was performed by two independent investigators at the beginning and end of each dosing regimen.
Results: Lornoxicam 8 mg b.d. caused significantly less mucosal injury than naproxen 500 mg b.d. in the stomach/duodenal bulb, as well as in the mid/distal duodenum.
Conclusion: These findings may have favourable implications for lornoxicam in the clinical setting, if this dose provides optimal control of arthritic pain.     

Polyketal Nanoparticles Co-Loaded With miR-124 and Ketoprofen for Treatment of Rheumatoid Arthritis

Ketoprofen, a non-steroidal anti-inflammatory drug, can effectively relieve pain associated with arthritis, and microRNA-124 (miR-124) can inhibit the progression of the disease. In this study, poly (cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK) nanoparticles (NPs) co-loaded with ketoprofen and miR-124 were successfully prepared using an emulsified solvent evaporation method. The co-loaded NPs exhibited a mean particle diameter of 160 nm. The acid sensitivity of the NPs was determined through in vitro release experiments. An adjuvant-induced arthritis rat model of arthritis was established for evaluating the pharmacodynamics of the NPs through clinical scoring and degree of swelling. The PCADK NPs exhibited more potent pharmacodynamic effects owing to the acid-sensitive properties of the carrier materials, compared with Poly (lactic-co-glycolic acid) (PLGA) NPs. Furthermore, PCADK co-loaded NPs exhibited superior anti-inflammatory effects compared to NPs loaded with either miR-124 or ketoprofen alone. In conclusion, co-delivery of ketoprofen and miR-124 through NPs is a promising strategy for the treatment of arthritis.     

Carvedilol can attenuate histamine-induced paw edema and formaldehyde-induced arthritis in rats without risk of gastric irritation

Background and aimRheumatoid arthritis treatment aims to control joint damage and any associated complications such as cardiovascular disease. Most anti-inflammatory drugs have a high tendency to cause gastro-intestinal irritation. The present study is designed to investigate the anti-inflammatory effect of carvedilol and to study its effect on gastric mucosa.Experimental approachLornoxicam (1.3 mg/kg) or carvedilol (10 mg/kg) was administrated orally 1 h before histamine injection into animals of a histamine-induced paw edema model and orally daily for 11 days into animals of a formaldehyde-induced arthritis model. Tumor necrosis factor-α and prostaglandin E₂ were measured in animals of the formaldehyde-induced arthritis model. The effect of lornoxicam and carvedilol on gastric mucosa was assessed in normal rats and after induction of cold stress ulcer.ResultsCarvedilol succeeded in reducing hind paw edema in both histamine-induced paw edema and formaldehyde-induced arthritis and in reducing the elevated level of tumor necrosis factor-α and prostaglandin E₂ nearly with near equal efficacy compared with lornoxicam. Carvedilol did not show any ulcerative effect on the gastric mucosa of normal rats, and its use was associated with an improvement of both the gross and histopathological pictures of gastric ulcers in animals of the cold stress ulcer model compared with lornoxicam treated rats.ConclusionThe current findings support the use of carvedilol both in the management of inflammation as well as the prevention of cardiovascular complications in rheumatoid arthritis patients. The use of carvedilol was not associated with any gastro-intestinal tract irritation.     

Niosomal gel for site-specific sustained delivery of anti-arthritic drug: in vitro-in vivo evaluation

Celecoxib, a selective COX-2 inhibitor is commonly used in the treatment of arthritis. Recently, cardiotoxic effects associated with conventional modes of delivery of celecoxib have made it pertinent to develop alternate dosage forms capable of selectively delivering the drug topically to affected joints. The aim of the present study was to prepare and characterize niosomal gel formulation for sustained and site-specific delivery of celecoxib. Celecoxib loaded niosomes were prepared and characterized in vitro, ex-vivo and in vivo. The results of organ localization (deep skin layer + muscle) study showed that niosomal gel provided 6.5 times higher drug deposition as compared to carbopol gel (195.2+/-8.7 and 30.0+/-1.5 microg, respectively). The muscle to plasma concentration ratio for niosomal gel formulation was six (2.16+/-0.12 microg/g vs. 0.34+/-0.01 microg/ml) and for carbopol gel it was one (0.36+/-0.01 microg/g vs. 0.43+/-0.02 microg/ml). Biological effectiveness of optimized formulation was evaluated using carrageenan induced rat paw edema model. The application of niosomal gel produced significant reduction of rat paw edema as compared to that after application of conventional gel indicating better skin permeation and deposition of celecoxib from niosomes. The results of the present study demonstrated niosomal gel formulation possess great potential for enhanced skin accumulation, prolonging drug release and improving the site specificity of celecoxib.     

Effects of lornoxicam, piroxicam, and meloxicam in a model of thermal hindpaw hyperalgesia induced by formalin injection in rat tail.

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used as analgesics. Although the results of clinical studies indicate considerable disparity in the analgesic efficacy of NSAIDs, the pre-clinical models generally used for the study of nociception do not allow a clear distinction to be made between the analgesic properties of agents belonging to this family. As clinical pain is characterized by hyperalgesia, we evaluated the effects of NSAIDs with similar chemical structures but different selectivities for cyclo-oxygenase (COX)-1 and COX-2 in a new behavioural model of central hyperalgesia in rats. We assessed the effects of lornoxicam, piroxicam, and meloxicam on the reduction of hindpaw nociceptive thresholds to thermal stimulation produced by a 10% formaldehyde (formalin) injection into rat tail. Each drug was administered intraperitoneally (i.p.) at its ED(50)for the anti-inflammatory effect (namely the inhibition of carrageenan-induced hindpaw oedema). At this dose (1.3 mg kg(-1), 1.0 mg kg(-1), and 5.8 mg kg(-1), respectively), lornoxicam, piroxicam, and meloxicam produced the same anti-inflammatory effect, did not modify thermal nociceptive thresholds, and significantly reduced the hyperalgesia. However, only lornoxicam was fully effective for prevention of hyperalgesia. Our results indicate a dissociation between the anti-inflammatory and the anti-hyperalgesic activity of NSAIDs, where the latter seems to be more evident after the block of both COX-1 and COX-2. Finally, they suggest that our experimental model of thermal hindpaw hyperalgesia can be effectively utilized to assess the ability of different drugs to reduce central sensitization, and thus hyperalgesia.     

Influence of cryogenic grinding on properties of a self-emulsifying formulation

Recently, self-emulsifying drug delivery systems (SEDDS) have been developed as a method to deliver lipophilic drugs. Gelucire 44/14 is an excipient, from the lauroyl macrogolglycerides family, producing a fine oil-in-water emulsion when introduced into an aqueous phase under gentle agitation as SEDDS, improving thereby solubility of poorly water-soluble drugs and their bioavailability. The aims of this study were to process Gelucire 44/14 into a powder by cryogenic grinding to produce solid oral dosage forms and to investigate influence of this process on different properties of a formulation made of Gelucire 44/14 and ketoprofen (90/10). Cryogenic grinding produced Gelucire 44/14 in a powder form and this process did not change its physical properties, emulsification capacities and dissolution performances of the formulation tested. However, interactions took place between ketoprofen and Gelucire 44/14 with a decrease of the melting peak and a reduction of the droplet size of the formed emulsion. The influence of drug-Gelucire 44/14 interactions must be investigated case by case in any formulations.     

Efficacy and tolerability of lornoxicam versus tramadol in postoperative pain.

This randomized double-blind study compared the analgesic efficacy and tolerability of intramuscular lornoxicam and tramadol in 76 patients with moderate to unbearable pain following arthroscopic reconstruction of the anterior cruciate ligament using the patella bone-tendon-bone technique. Patients receiving a single dose of lornoxicam 16 mg experienced significantly greater total pain relief than patients receiving tramadol 100 mg over the following 8 hours. Lornoxicam had greater analgesic efficacy than tramadol in patients with moderate baseline pain but was of equivalent efficacy in those with severe/unbearable baseline pain. Fewer patients in the lornoxicam group required rescue medication (58% vs. 77%, respectively). Patients' global impression of efficacy showed lornoxicam to be superior to tramadol with 82% and 49% of patients, respectively, rating treatment as good, very good, or excellent. Following multiple-dose administration of lornoxicam (8 mg tid) or tramadol (100 mg tid) for 3 days, efficacy profiles similar to those following a single dose were obtained. Thus, slightly fewer patients in the lornoxicam group required rescue medication, and patients' global impression of efficacy again favored lornoxicam. Adverse events were reported by 38 of the 76 patients and were mainly mild to moderate in severity. Significantly fewer patients reported one or more adverse events with lornoxicam than with tramadol (14 vs. 24, respectively). Thus, intramuscular lornoxicam offers a useful alternative to tramadol for the treatment of moderate to severe postoperative pain.     

Comparative bioavailability of lornoxicam as single doses of quick-release tablet, standard tablet and intramuscular injection: a randomized, open-label, crossover phase I study in healthy volunteers

BACKGROUND AND OBJECTIVE: Lornoxicam is an NSAID used to obtain short-term relief of acute mild to moderate pain and symptomatic relief of pain and inflammation in rheumatoid arthritis and osteoarthritis. The aim of this study was to compare and evaluate the pharmacokinetic parameters of lornoxicam 8 mg as quick-release (QR) tablet, standard tablet (ST) and intramuscular injection (IM). METHODS: Eighteen healthy volunteers (9 male, 9 female; average age 26.9 (SD 3.0) years; average body mass index 21.8 (SD 2.3) kg/m2 were randomized to three different treatment groups. Subjects received a single 8-mg dose of each lornoxicam formulation in a three-way crossover design on days 1, 8 and 15. Lornoxicam plasma concentrations were obtained from baseline to 24 hours using high-pressure liquid chromatography. The pharmacokinetic parameters area under the plasma concentration-time curve from zero to infinity (AUCinfinity), maximum plasma concentration (Cmax), time to maximum plasma concentration (tmax), terminal half-life (t1/2)) and mean residence time (MRT) were calculated. RESULTS: Lornoxicam-QR was comparable with lornoxicam-ST and lornoxicam-IM regarding AUCinfinity, t1/2 and MRT. The AUCinfinity ratio (90% CI) was 1.07 (0.94, 1.20) for lornoxicam-QR/lornoxicam-ST and 1.10 (0.97, 1.24) for lornoxicam-QR/lornoxicam-IM. Cmax and tmax did not differ between lornoxicam-QR and lornoxicam-IM (p=0.66 and 0.07, respectively). Both lornoxicam-QR and lornoxicam-IM showed significantly shorter tmax and significantly higher Cmax values than lornoxicam-ST. CONCLUSION: Lornoxicam-QR and lornoxicam-IM did not differ with respect to AUCinfinity, Cmax and tmax, but both lornoxicam-QR and lornoxicam-IM showed significantly shorter tmax and significantly higher Cmax values than lornoxicam-ST.     

Novel sustained-release fast-disintegrating multi-unit compressed tablets of lornoxicam containing Eudragit RS coated chitosan-alginate beads

Novel fast-disintegrating multi-unit tablets (FDMUTs) were prepared to modify the release of lornoxicam (a potent non-steroidal anti-inflammatory drug with a short half-life) as well as to combine the advantages of multi-unit systems with the cost-effectiveness of compressed tablets. The proposed FDMUTs consisted of sustained-release lornoxicam beads directly compressed with fast-disintegrating component, containing amorphous solid dispersion of lornoxicam, anticipating rapid drug release that starts in the stomach to rapidly alleviate the painful symptoms and continues in the intestine to maintain extended analgesic effect. Initially, calcium-alginate and chitosan-alginate beads containing lornoxicam were prepared. Then, the erosion of selected beads formulation was suppressed by treatment with Eudragit RS either through polymer-reinforcement or beads coating. The beads, which elicited appropriate sustainment of lornoxicam release, were directly compressed with fast-disintegrating components to form FDMUTs. The release characteristics of the original beads were maintained after compression which indicates that the adopted compression process did not induce mechanical damage to the beads or coating. All of the prepared FDMUTs demonstrated acceptable physical properties that complied with compendial requirements. Release studies, performed in simulated gastric and intestinal fluids used in sequence to mimic the gastrointestinal transit, illustrate that the FDMUTs containing 8?mg lornoxicam equally distributed between the sustained-release beads and the fast-release component, showed the desired release profile.     

Moisture Uptake of Polyoxyethylene Glycol Glycerides Used as Matrices for Drug Delivery: Kinetic Modelling and Practical Implications

Purpose

Gelucire 50/13, a polyoxyethylene glycol glyceride mixture, has been widely used in drug delivery, but its moisture uptake behaviour is still poorly understood. In this study, the effects of relative humidity, temperature, and drug incorporation on the moisture uptake of Gelucire are reported in relation to their practical implications for preparation of solid dispersions using this material.

Methods

DVS combined with kinetics modelling was used as the main experimental method to study the moisture uptake behaviour of Gelucire. Thermal and microscopic methods were employed to investigate the effect of moisture uptake on the physical properties of the material and drug loaded solid dispersions.

Results

The moisture uptake by Gelucire 50/13 is temperature and relative humidity dependent. At low temperatures and low relative humidities, moisture sorption follows a GAB model. The model fitting indicated that at high relative humidities the sorption is a complex process, potentially involving PEG being dissolved and the PEG solution acting as solvent to dissolve other components.

Conclusion

Careful control of the storage and processing environmental conditions are required when using Gelucire 50/13. The incorporation of model drugs not only influences the moisture uptake capacity of Gelucire 50/13 but also the solidification behaviour.     

Anti-hyperalgesic and anti-inflammatory effects of Ketorolac Tromethamine gel using pulsed ultrasound in inflamed rats

The aim of this study was to determine if a Ketorolac Tromethamine (KT) gel solution could be administered in vivo via phonophoretic transdermal delivery using pulsed ultrasound by examining its anti-hyperalgesic and anti-inflammatory effects in a rat carrageenen inflammation model. 1% carrageenan was injected into the plantar surface of the right hindpaw of a rat, and anti-hyperalgesic and anti-inflammatory effects of KT via phonophoretic transdermal delivery were examined. The changes in the mechanical and thermal hyperalgesia, nociceptive flexor reflex (NFR), as well as the swelling changes were determined. According to the anti-hyperagesia and anti-inflammation tests, which were used to determine the change in the pain thresh-old, NFR and swelling showed that the group given the phonophoretic transdermal delivery of KT exhibited significantly more noticeable anti-hyperalgesic and anti-inflammatory effects than those treated with the simple application of a KT gel. The transdermal application of KT gel using phonophoresis had significant anti-hyperalgesic and anti-inflammatory effects. These findings suggest that the transdermal administration of a KT gel using phonophoresis using pulsed ultrasound might be useful for treating acute inflammation and pain.     

Preparation and in vivo evaluation of indomethacin loaded true nanoemulsions

Indomethacin, a potent nonsteroidal anti-inflammatory drug, has been used in the treatment of various kinds of pains, inflammation and arthritis. However, oral administration of indomethacin produces serious gastrointestinal adverse effects. Therefore the aim of the present investigation was to evaluate the anti-inflammatory effects, skin irritation, activation energy and histopathology of indomethacin from transdermally applied true nanoemulsion. The anti-inflammatory effects of true nanoemulsions were compared with marketed Indobene^® gel on carrageenan-induced paw edema in rats. Skin irritation tests were performed on Wistar rats for 14 days. The % inhibition value after 12 h application was significant for optimized formulation F6 (83) as compared to marketed Indobene^® gel (P<0.01). Results of skin irritation test indicated that developed true nanoemulsion is safe for human use. The significant decrease in activation energy (1.396 kcal/mol) for indomethacin across rat skin indicated that the stratum corneum lipid bilayers were significantly disrupted (P<0.05). From these results it was concluded that the developed nanoemulsion have great potential for transdermal application of indomethacin.     

Tyrosinase inhibitor-loaded microsponge drug delivery system: new approach for hyperpigmentation disorders

Objective: The aim of the present investigation was to design and formulate appropriate form of glabridin, using microsponge drug delivery system. Method: Microsponges were prepared by emulsion solvent evaporation method and characterized by drug loading, infrared spectroscopy and scanning electron microscopy. In?vitro diffusion studies of gel formulation were performed using ethanol: phosphate buffer (1:1) mixture as receptor medium. Animal studies were carried out using brownish guinea pigs with UV-induced pigmentation model. Results: Prepared microsponges were predominantly yellowish, free-flowing and spherical in shape. The infrared spectra revealed the absence of drug polymer interaction. Scanning electron microscopy (SEM) and porosity studies confirmed spherical and porous nature. In?vitro release studies data depicted highest correlation with Higuchi treatment. Animal studies also supported the better depigmenting activity as compared to plain gel. Conclusion: Glabridin microsponge-loaded gel could be efficacious in treating various hyperpigmentation disorders.     

Formulation and ex vivo evaluation of rofecoxib gel for topical application

The potential gastrointestinal disorders associated with oral administration of rofecoxib can be avoided by delivering the drug to the inflammation site at a sustained, concentrated level over an extended period of time. Hydroxypropylmethylcellulose (HPMC), sodium alginate and Carbopol 940 were used in an attempt to develop topical gel formulations of rofecoxib. The effects of polymer composition on the rate of drug release from the gel formulations were examined through cellulose membrane mounting on a Keshary-Chien diffusion cell. The effects of initial drug concentration and viscosity on the permeation rate of rofecoxib from the gel formulations were evaluated using rat epidermis at 37 +/- 0.5 degrees C. The anti-inflammatory activity of the rofecoxib gel formulation was evaluated using the rat hind paw edema model. The gel formulation consisting of 4% w/w sodium alginate-Carbopol 940 at 3:1 ratio was found to be suitable for topical application based on in vitro evaluation and ex vivo permeation studies. The drug permeation rate increased with an increase of the initial drug concentration in gels up to 25% w/w. An inverse relationship was observed between the in vitro drug release rate/ex vivo permeation rate and viscosity of the gel formulations. The anti-inflammatory activity of 4% w/w sodium alginate-Carbopol 940 gel containing 25% w/w rofecoxib in the rat hind paw edema model reveals that the drug was delivered to the inflammation site at a controlled level over a period of 6 h. These results suggest the feasibility of the topical gel formulation of rofecoxib.     

Shape,optimization and in vitro evaluation of colon-specific multi-particulate system based on low-methoxy amidated pectin and polycarbophil

Natural polysaccharides are widely used for development of colon-specific drug delivery systems. The present study was carried out to develop multi-particulate calcium pectinate (Ca-pectinate) formulations for colon-targeted delivery of lornoxicam. The formulations were developed using a combination of polycarbophil and low-methoxy amidated pectin. The beads were prepared using an ionotropic gelation technique. The effects of the polycarbophil and low-methoxy amidated pectin concentrations on the beads characteristics, encapsulation efficiency, swelling study and drug release performance were investigated. The optimized formulation was evaluated for its morphological characteristics. The in vitro drug release of the optimized formulation over a period of 12 h was 96.78 ± 1.35 %. The concentration of the polycarbophil was a decisive factor in sustaining drug release in the colon. The study revealed that optimized Ca-pectinate beads prepared with polycarbophil can efficiently encapsulate lornoxicam. It also showed that these beads can potentially be used for colon-specific delivery of lornoxicam.     

Design and evaluation of a novel transdermal patch containing diclofenac and teriflunomide for rheumatoid arthritis therapy

The aim of this study was to design a compound transdermal patch containing diclofenac (DA) and teriflunomide (TEF) for the treatment of rheumatoid arthritis (RA). The various organic amines salts of DA were prepared and their forming was confirmed using DSC and FTIR. The percutaneous permeation of organic amines salt of DA was investigated in vitro using a two-chamber diffusion cell with excised rabbit skin as transdermal barrier. The formulation of the patch was optimized in terms of the concentration of percutaneous permeation enhancer and the loading dose of drugs. The pharmacokinetic behavior of the optimal formulation was studies in rabbits and the anti-inflammatory and analgesic effects of the optimal patch were evaluated with the adjuvant arthritis model in rats and the pain model in mice, respectively. The result showed that skin penetration of diclofenac-triethylamine (DA-TEtA) salt was better than other organic amine salts. Based on previous study of our laboratory, teriflunomide-triethylamine (TEF-TEtA) significantly enhanced the skin permeation of TEF. 10% of azone (AZ) was the best enhancer for the two drugs. The optimal patch formulation was composed of 2% of TEF-TEtA, 6% of DA-TEtA and 10% of AZ. The cumulative permeated amount of DA-TEtA in vitro was comparable with that of the commercial diclofenac-diethylamine (DA-DEtA) patch. The absolute bioavailability of TEF-TEtA was 42%, which could achieve the therapeutic drug levels. In animal study, the optimized compound patch containing DA-TEtA and TEF-TEtA displayed significant anti-inflammatory and analgesic effect, which indicated the potential of the compound patch.     

喷雾干燥氯诺昔康自微乳化制剂在兔体内的生物利用度

以氯诺昔康片剂为参比制剂,考察了自制喷雾干燥氯诺昔康自微乳化制剂在兔体内的相对生物利用度.以吡罗昔康为内标,采用高效液相色谱法测定兔血浆中的氯诺昔康.6只家兔分别灌胃给予氯诺昔康的片剂或喷雾干燥自微乳化制剂,结果显示,其AUC分别为16 304和26 328 ng·h·ml-1,cmax分别为824和1788 ng/ml,tmax分别为7.0和3.0 h.配对t检验分析表明AUC和cmax具有显著性差异(P＜0.05),tmax具有极显著性差异(P＜0.01),自微乳化制剂的相对生物利用度为161.5％.