In vitro/in vivo correlation of prolonged release dosage forms containing diltiazem HCl

Six preparations were considered: three multiple unit dosage forms (micropellets in capsules) (D, E and G) and one matrix tablet (B) were experimental prolonged release formulations, two non-disintegrating tablets (A and C) were commercial products. The in vitro dissolution behaviour of the differing formulations was investigated using the USP XXII paddle apparatus. The in vivo study was effected on a panel of 12 healthy volunteers. The two commercial tablets (A and C) showed mean dissolution time (MDT) of 1.34 and 1.44 h and t_d of 91 and 92 min, respectively; for prolonged release formulations (B, E, D, and G) MDT ranged between 2.28 and 4.23 h and t_d between 149 and 291 min. The mean residence time (MRT) was 8.68 and 6.47 h for tablets A and C, respectively; it ranged between 9.62 and 10.24 h for the multiple unit formulations E, D, and G and was 11.27 h for matrix B. Formulation B also showed the higher apparent elimination half-life t_1/2 (7.12 h), while apparent t_1/2 for all the other formulations were very similar, ranging between 5.04 and 5.28 h. High variability between the various formulations was found for C_max and AUC values, and no relationships could be established with the type of formulation. An in vitro/in vivo correlation was found for all the formulations examined on the basis of analogous parameters (MDT and MRT); (r = 0.83, p <0.05). In a few cases the Wagner-Nelson deconvolution method was applied to individual plasma level versus time curves and the corresponding absorption curves were obtained. In these cases the in vitro/in vivo correlation was tested on the basis of the comparison of the in vivo absorption curves with the in vitro dissolution profiles. This was accomplished using the ‘Levy's plot’ (per cent released versus per cent absorbed) approach and provided further support for the correlation found.     

Nanotransfersomes-loaded thermosensitive in situ gel as a rectal delivery system of tizanidine HCl: preparation,in vitro and in vivo performance

The purpose of the current study was to develop tizanidine HCl (TIZ; a myotonolytic agent used for treatment of spasticity) loaded nanotransfersomes intended for rectal administration, aiming to bypass the hepatic first-pass metabolism. TIZ-loaded nanotransfersomes were prepared by thin-film hydration method followed by characterization for various parameters including entrapment efficiency, vesicle diameter, in vitro release and ex vivo permeation studies. Transfersomal formulation composed of phosphatidylcholine and Tween 80 at a weight ratio of (85:15) gave a satisfactory results. It exhibited encapsulation efficiency of 52.39%, mean diameter of 150.33?nm, controlled drug release over 8?h and good permeation characteristics. Optimum formula was then incorporated into Pluronic-based thermoreversible gel using hydroxypropyl methylcellulose (HPMC) as a mucoadhesive polymer. Pharmacokinetic study was performed by rectal administration of transfersomes-loaded in situ gel to rabbits and compared with oral drug solution and rectal TIZ in situ gel. The pharmacokinetic study revealed that the transfersomal formulation successively enhanced the bioavailability of TIZ by about 2.18-fold and increased t_1/2 to about 10?h as compared to oral solution. It can be concluded that encapsulation of TIZ into nanotransfersomes can achieve a dual purpose of prolonged TIZ release and enhanced bioavailability and so may be considered as a promising drug delivery system for the treatment of spasticity.     

Controlled release effervescent buccal discs of buspirone hydrochloride: in vitro and in vivo evaluation studies

Abstract

In the present study controlled release effervescent buccal discs of buspirone hydrochloride (BS) were designed using HPMC as rate controlling and bioadhesive polymer by direct compression method. Sodium bicarbonate and citric acid were used in varying amounts as effervescence forming agents. Carbon dioxide evolved due to reaction of sodium bicarbonate and citric acid was explored for its potential as buccal permeation enhancer. The designed buccal discs were evaluated for physical characteristics and in vitro drug release studies. Bioadhesive behavior of designed buccal discs was assessed using texture analyzer. In vivo animal studies were performed in rabbits to study bioavailability of BS in the designed buccal discs and to establish permeation enhancement ability of carbon dioxide. It was observed that effervescent buccal discs have faster drug release compared to non-effervescent buccal discs in vitro and effervescent buccal discs demonstrated significant increase in bioavailability of drug when compared to non-effervescent formulation. Hence, effervescent buccal discs can be used as an alternative to improve the drug permeation resulting in better bioavailability. However, the amount of acid and base used for generation of carbon dioxide should be selected with care as this may damage the integrity of bioadhesive dosage form.     

Development and evaluation of dual controlled release microballoons containing riboflavin and citric acid: in vitro and in vivo evaluation

The objective of this work was to optimize the incorporation of citric acid (CA) in the gastroretentive microballoons containing riboflavin (RF) in order to achieve dual controlled release system and consequently enhance the bioavailability of RF. Microballoons of 739?±?1.9?µm containing RF–CA were prepared by modified emulsion solvent diffusion method and were evaluated both for in vitro and in vivo performance. RF–CA microballoons with 22.8% RF and 37.2% CA entrapped in the shell matrix composed of Eudragit® S 100 and HPMCK4M and in vitro buoyancy of 86.0?±?0.88% (RCM3) was selected for further studies. RCM3 exhibited biphasic, pH-dependent in vitro dual controlled release of RF (0.9933–0.9962) and CA (0.996–0.9984) beyond 1?h in both simulated fasted and fed state conditions. RCM3 was able to achieve higher mean plasma concentrations than reference formulation RM2 (RF microballoon) both in fed and fasted states in rabbits. The mean AUC_0–24 estimate of RCM3 was 55% higher in fasted state (p?<?0.01) and about 51% higher in fed state (p?<?0.05) relative to mean AUC_0–24 from RM2 formulation. Conclusively, enhancement in RF in the presence of CA along the entire plasma level curve suggests a possibility of reduction in dosing frequency. This controlled release drug delivery system of RF, where CA is incorporated in the microballoons can be easily encapsulated in capsule dosage form negating the need of CA solution as vehicle for administration of RF microballoons.     

基于粉末直接压片工艺的硝苯地平缓释片：制备、体外释放度及比格犬体内药动学评价

目的选用粉末直接压片工艺,以羟丙基甲基纤雏素为骨架材料制备日服1次的硝苯地平缓释片。方法建立24h的释放度测定方法并进行硝苯地平缓释片的体外评价;应用液相色谱-质谱联用技术研究缓释片在比格犬体内药代动力学,与市售参比制剂对比并计算相对生物利用度。结果受试制剂和参比制剂有相似的药代动力学参数,相对生物利用度为（100．9±12．4）％;药物体外累积释放百分数与体内吸收百分数有较好的相关性,r=0．9625。结论本工艺制得的硝苯地平缓释片可以达到缓释24h的要求。     

Microencapsulation of budesonide with dextran by spray drying technique for colon-targeted delivery: an in vitro/in vivo evaluation in induced colitis in rat

The aim of this study was developing colon targeted-delivery of budesonide for ulcerative colitis. Microcapsules were prepared using spray drying technique by different drug-to-dextran ratios and three molecular weights (MWs) of polymer. Differential scanning calorimetry, X-ray diffraction (XRD), drug release and loading efficiency of microcapsules were studied. In vivo efficacy of the selected formulation prepared by 1?:?10 drug-to-polymer ratio and dextran with MW 500?000 (D10M500) against acetic acid-induced colitis in rats was evaluated and compared to the control and reference groups (mesalasine and budesonide suspensions). The results showed that D10M500 microcapsules could target the drug to colon and its efficacy in reducing macroscopic damage score was higher than mesalasine suspension. Treatment with D10M500 decreased the scores of crypt damage and total colitis significantly compared to the control group which just received the vehicle and the groups treated with mesalasine and budesonide suspension which could not reduce the colitis parameters significantly.     

Development of a drug-in-adhesive patch combining ion pair and chemical enhancer strategy for transdermal delivery of zaltoprofen: pharmacokinetic,pharmacodynamic and in vitro/in vivo correlation evaluation

The aim of the study was to develop a drug-in-adhesive patch system for transdermal delivery of zaltoprofen (ZAL). The formulation was designed in combination with the ion pair and chemical enhancer strategy. Seven organic amines were chosen as counter ions, and the prepared ion pairs were characterized by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The in vivo pharmacokinetic performance of ZAL was studied on rabbits following transdermal and intravenous administration. A deconvolution method was applied to determine the correlation between the in vitro permeation and the in vivo absorption. Acetic acid-induced writhing response was conducted on mice to evaluate the analgesic effect. In vitro permeation results showed that both ion pairs and chemical enhancers were effective in modulating ZAL skin permeation from patches. The enhancement ratio was negatively correlated to the polar surface area (PSA) of counter ions, and was positively correlated to the octanol–water partition coefficient (log K_o/w) of chemical enhancers, respectively. The optimized formulation contained 10% (w/w) ZAL-triethylamine and 10% (w/w) isopropyl myristate, with DURO-TAK® 87-4098 as the pressure sensitive adhesive matrix. Furthermore, the in vitro permeation data were well correlated with the in vivo absorption data. The analgesic effect of the optimized patch was comparable to the commercial indometacin plasters. In conclusion, it was feasible for transdermal delivery of ZAL by the synergistic action of ion pair and chemical enhancer, and the in vitro permeation data were indicative of the in vivo performance for the developed patches.     

Enhanced bioavailability of buspirone hydrochloride via cup and core buccal tablets: Formulation and in vitro/in vivo evaluation

This work aims to prepare sustained release buccal mucoadhesive tablets of buspirone hydrochloride (BH) to improve its systemic bioavailability. The tablets were prepared according to 5 × 3 factorial design where polymer type was set at five levels (carbopol, hydroxypropyl methylcellulose, sodium alginate, sodium carboxymethyl cellulose and guar gum), and polymer to drug ratio at three levels (1:1, 2:1 and 3:1). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h) and time for release of 50% BH (T_50%) were chosen as dependent variables. Additional BH cup and core buccal tablets were prepared to optimize BH release profile and make it uni-directional along with the tablets mucoadhesion. Tablets were evaluated in terms of content uniformity, weight variation, thickness, diameter, hardness, friability, swelling index, surface pH, mucoadhesion strength and time and in vitro release. Cup and core formula (CA10) was able to adhere to the buccal mucosa for 8 h, showed the highest Q8h (97.91%) and exhibited a zero order drug release profile. Pharmacokinetic study of formula CA10 in human volunteers revealed a 5.6 fold increase in BH bioavailability compared to the oral commercial Buspar^® tablets. Conducting level A in vitro/in vivo correlation showed good correlation (r² = 0.9805) between fractions dissolved in vitro and fractions absorbed in vivo.     

Multivesicular liposomes for sustained release of naltrexone hydrochloride: design,characterization and in vitro/in vivo evaluation

Multivesicular liposomes containing naltrexone hydrochloride (DepoNTX) was prepared by using the traditional DepoFoam technology and the key formulation factors on encapsulation efficiency and particle size were investigated. A morphological characterization and in vitro/in vivo release assay was also carried out. NTX was successfully encapsulated in DepoNTX with good yield and showing the spherical, smooth and multivesicular characteristics of particle by a light microscope. The in vitro studies in human plasma and sodium chloride showed that 80–85% of NTX encapsulated in MVLs released slowly from particles over 5 days. In vivo study, after a single dose of 2.0?mg/kg of DepoNTX formulation administered subcutaneously in rats, plasma NTX levels were maintained at a relatively constant level above 10?ng/mL for approximately 120?h, while after administered NTX solution, NTX level was quickly decreased below 10?ng/mL within 20?h. The results of the study demonstrated that DepoNTX was very promising candidate for sustained release delivery of naltrexone hydrochloride.     

Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design,characterization, in vitro and in vivo evaluation

Abstract

Naringenin (NRG), predominant flavanone in grapefruits, possesses anti-inflammatory, anti-carcinogenic, hepato-protective and anti-lipid peroxidation effects. Slow dissolution after oral ingestion due to its poor solubility in water, as well as low bioavailability following oral administration, restricts its therapeutic application. The study is an attempt to improve the solubility and bioavailability of NRG by employing self-nanoemulsifying drug delivery technique. Preliminary screening was carried out to select oil, surfactant and co-surfactant, based on solubilization and emulsification efficiency of the components. Pseudo ternary phase diagrams were constructed to identify the area of nanoemulsification. The developed self-nanoemulsifying drug delivery systems (SNEDDS) were evaluated in term of goluble size, globule size distribution, zeta potential, and surface morphology of nanoemulsions so obtained. The TEM analysis proves that nanoemulsion shows a droplet size less than 50?nm. Freeze thaw cycling and centrifugation studies were carried out to confirm the stability of the developed SNEDDS. In vitro drug release from SNEDDS was significantly higher (p?<?0.005) than pure drug. Furthermore, area under the drug concentration time-curve (AUC_0–24) of NRG from SNEDDS formulation revealed a significant increase (p?<?0.005) in NRG absorption compared to NRG alone. The increase in drug release and bioavailability as compared to drug suspension from SNEDDS formulation may be attributed to the nanosized droplets and enhanced solubility of NRG in the SNEDDS.     

Osmotically controlled pulsatile release capsule of montelukast sodium for chronotherapy: Statistical optimization,in vitro and in vivo evaluation

Abstract

The purpose of present study was to design, optimize and evaluate osmotically controlled pulsatile release capsule (PRC) of montelukast sodium (MKS) for the prevention of episodic attack of asthma in early morning and associated allergic rhinitis. Assembly of the capsular systems consisted of push, active and plug tablet arranged from bottom to top in hard gelatin capsule. The capsule system was coated with a semi-permeable membrane of cellulose acetate and drilled towards plug side in cap. A three-factor, three-level central composite design (CCD) with α?=?1 was introduced to execute the experiments and quadratic polynomial model was generated to predict and assess the independent variables with respect to the dependent variables. The composition of optimal formulation was determined as weight of push tablet 138?mg (coded value: +0.59), plug tablet 60?mg (coded value: +0.49) and coating weight gain of 8.4?mg (coded value: ?0.82). The results showed that the optimal formulation of PRCs had lag time of 4.5?h, release at 6 and 12?h are 61.95% and 96.29%, respectively. The X-ray radiographic imaging study was carried out to monitor the in vivo behavior of developed barium sulfate-loaded PRCs in rabbits under fasting conditions. In vivo pharmacokinetic study revealed T_max of 2?h for marketed tablets; however 7?h for PRCs with initial lag time of 4?h. Thus designed capsular system may be helpful for patients with episodic attack of asthma in early morning and associated allergic rhinitis.     

Comparative study of kanamycin sulphate microparticles and nanoparticles for intramuscular administration: preparation in vitro release and preliminary in vivo evaluation

Kanamycin sulphate (KS) is a Mycobacterium tuberculosis protein synthesis inhibitor. KS is polycationic, a property responsible for KS poor oral absorption half-life (2.5?h) and rapid renal clearance, which results in serious nephrotoxicity/ototoxicity. The current study aimed to develop KS-loaded PLGA vitamin-E-TPGS microparticles (MPs) and nanoparticles (NPs) to reduce the dosing frequency and dose-related adverse effect. In vitro release was sustained up to 10 days for KS PLGA–TPGS MPs and 13 days for KS PLGA–TPGS NPs in phosphate-buffered saline (PBS) pH 7.4. The in vivo pharmacokinetic test in Wistar rats showed that the AUC_0–∞ of KS PLGA–TPGS NPs (280.58?μg/mL*min) was about 1.62-fold higher than that of KS PLGA–TPGS MPs (172.30?μg/mL*min). Further, in vivo protein-binding assay ascribed 1.20-fold increase in the uptake of KS PLGA–TPGS NPs through the alveolar macrophage (AM). The studies, therefore, could provide another useful tool for successful development of KS MPs and NPs.     

Enhanced transdermal delivery of meloxicam by nanocrystals: Preparation,in vitro and in vivo evaluation

 Meloxicam (MLX) is efficient in relieving pain and inflammatory symptoms, which, however,is limited by the poor solubility and gastrointestinal side effects. The objective of thisstudy is to develop a nanocrystal formulation to enhance transdermal delivery of MLX. MLXnanocrystals were successfully prepared by the nanoprecipitation technique based on acidbaseneutralization. With poloxamer 407 and Tween 80 (80/20, w/w) as mixed stabilizers,MLX nanocrystals with particle size of 175 nm were obtained. The crystalline structure ofMLX nanocrystals was confirmed by both differential scanning calorimetry and X-ray powderdiffractometry. However,the nanoprecipitation process reduced the crystallinity of MLX.Nanocrystals increased both in vitro and in vivo transdermal permeation of MLX comparedwith the solution and suspension counterparts. Due to the enhanced apparent solubilityand dissolution as well as the facilitated hair follicular penetration, nanocrystals present ahigh and prolonged plasma MLX concentration. And 2.58- and 4.4-fold increase in AUC0→24hwas achieved by nanocrystals comparing with solution and suspension, respectively. In conclusion,nanocrystal is advantageous for transdermal delivery of MLX.     

Oral bioavailability enhancement of vinpocetine using self-microemulsifying drug delivery system containing long chain triglycerides: Preparation and in vitro/in vivo evaluation

Vinpocetine, a widely used neurotropic agent, has low oral bioavailability due to its poor solubility and extensive hepatic first-pass metabolism. In the present work, self-microemulsifying drug delivery systems (SMEDDS) employing long chain triglycerides (LCT) were successfully developed to increase vinpocetine’s solubility and reduce its hepatic first pass metabolism, thus enhancing its overall oral bioavailability. Maisine^?35-1 was chosen as the lipid component in the formulated SMEDDS as it showed the maximal vinpocetine solubility within different LCT tested. Feasibility of obtaining SMEDDS, containing Maisine^?35-1, together with Transcutol^®HP and either Cremophor^®EL or Tween 80, was evaluated using ternary phase diagrams. In vitro release studies performed in phosphate buffer of pH 7.4 illustrated that extent of vinpocetine release from SMEDDS was drastically higher than that obtained from commercial Cavinton^® tablets. The industrial usefulness of the developed SMEDDS was evaluated regarding their moisture sorption isotherms when filled into gelatin capsules and stored at different relative humidity. Vinpocetine’s optimal SMEDDS did not induce gross changes in the gastrointestinal mucosa of rats at the investigated dose. Moreover, it significantly improved the relative oral bioavailability of vinpocetine compared to Cavinton^® tablets. Accordingly, this study suggests that SMEDDS containing LCT under proper optimization and safety assessment can be effectively utilized for oral bioavailability enhancement of vinpocetine.     

Effect of mefenorex on 5-HT release: Studies in vitro on rat hypothalamic slices and in vivo by microdialysis

Mefenorex, used for 20 years as an anorexic drug, has not been studied so far with regard to its central mechanism of action, although its chemical structure suggests a serotonergic mechanism. In the present study, the effect of mefenorex on serotonin (5-HT) release was investigated both in vitro, on rat hypothalamic slices and in vivo, using microdialysis in the paraventricular (PVN)-ventromedian (VMM) hypothalamic area while mefenorex was applied locally by means of counterdialysis. In vitro, mefenorex increased the spontaneous release of ³H 5-HT from hypothalamic slices but not the electrically evoked release. This suggests a 5-HT releasing action of mefenorex not mediated through the terminal autoreceptor. The in vivo study confirmed the enhanced release and provided additional information. The delayed and modest increase of the 5-HT intracellular metabolite 5-HIAA may be indicative of an inhibition of reuptake. The dopaminergic system was also, but more modestly, activated by mefenorex. The increase in 5-HT release together with the inhibition of its reuptake may represent the main mechanism of action of mefenorex, and the secondary activation of the dopaminergic system may contribute in its anorexigenic effect at the level of the PVN-VMH area.     

Enhanced oral bioavailability of salmeterol by loaded PLGA microspheres: preparation,in vitro,and in vivo evaluation

The objective of the current study was to prepare microspheres of salmeterol (SM) using poly (lactide-co-glycolide) (PLGA) and assess its viability to enhance the oral bioavailability. Microspheres of SM were prepared by oil-in-water emulsion-solvent evaporation method. The formulations were characterized in encapsulation efficiency, particle size, zeta potential, and in vitro release. The prepared microspheres were found to be spherical in shape with smooth surface. The size of microspheres ranged from 14.7 to 16.5?µm. The polydispersity index (PDI) was 0.12?±?0.05 and the zeta potential was ?33.2?±?1.4?mV. In vitro release profile, SM was graduated released from the microspheres as time lapsed, suggesting that SM was well entrapped in SM-loaded PLGA microspheres. The model that fitted best for SM released from the microspheres was Higuchi equation. In vivo study, SM-loaded PLGA microspheres are thought to have the potential to maintain SM concentration within target ranges for a long time, decreasing side effects caused by concentration fluctuation, ensuring the efficiency of treatment and improving patient compliance by reducing dosing frequency.     

Formulation of zolmitriptan sublingual tablets prepared by direct compression with different polymers: In vitro and in vivo evaluation

First-pass metabolism can be overcome by sublingual drug delivery, and quick drug entry into the systemic circulation can be obtained. In certain diseases such as migraine therapy, taking fast pharmacological response is an important criteria. In this study, zolmitriptan sublingual tablets were prepared by direct compression method using different mucoadhesive polymers such as hydroxypropyl methyl cellulose, chitosan and sodium carboxy methyl cellulose at a concentration range of 0.5-5% to reduce flushing action of saliva and provide enough time for drug to be absorbed. Tablets were evaluated for the physical properties, and optimum formulations were chosen for in vivo studies to carry on sheep model. The tablets disintegrated rapidly, and dissolution tests revealed that zolmitriptan was dissolved from the formulation within the compendial limits. This especially showed us that the concentration range of polymers is in acceptable limit. It was also concluded that microcrystalline cellulose, spray-dried lactose and sodium starch glycolate are the appropriate excipient and formulated in good proportions. In vivo studies indicated that formulation containing 5% chitosan has the maximum C_max and AUC and minimum t_max values (p < 0.05). As a result, sublingual tablet administration of zolmitriptan formulated with appropriate excipients and especially with chitosan seems promising alternative to traditional routes.     

Identification of thymol phase I metabolites in human urine by headspace sorptive extraction combined with thermal desorption and gas chromatography mass spectrometry

Development of a novel highly sensitive headspace sorptive extraction (HSSE) method in combination with thermal desorption gas chromatography coupled to a mass spectrometer (TD-GC/MS) allowed the identification of thymol and several phase I metabolites in human urine. Combined with an enzymatic hydrolysis of glucuronated or sulphated phase II metabolites of thymol and of the respective phase I metabolites prior to analysis, even trace quantities of hitherto not detected thymol phase I metabolites could be identified in urine samples of test persons after oral administration of 50 mg thymol. It was proven, that human metabolism leads to a hydroxylation of the aromatic ring as well as of the iso-propyl side chain. Hydroxylation of the iso-propyl group results in the formation of the rather unstable p-cymene-3,8-diol and the corresponding dehydration product p-cymene-3-ol-8-ene which could be clearly detected in human urine samples. Furthermore, the aromatic hydroxylation products p-cymene-2,5-diol, its oxidation product p-cymene-2,5-dione and p-cymene-2,3-diol were also unambiguously identified by comparison with synthesized reference compounds.     

An alkylpolyglucoside surfactant as a prospective pharmaceutical excipient for topical formulations: The influence of oil polarity on the colloidal structure and hydrocortisone in vitro/in vivo permeation

There is a growing need for research into new skin- and environment-friendly surfactants. This paper focuses on a natural surfactant of an alkylpolyglucoside type, which can form both thermotropic and lyotropic liquid-crystalline phases. The aim of this study was to relate some physicochemical properties (characterised by polarisation and transmission electron microscopy, thermal analysis and rheology) of the three formulations based on cetearyl glucoside and cetearyl alcohol, to the results of in vitro and in vivo bioavailability of hydrocortisone (HC). The three formulations contained oils of different polarity (medium chain triglycerides: MG, isopropyl myristate: IPM and light liquid paraffin: LP), respectively. In vitro permeation was followed through the artificial skin constructs (ASC), while the parameters measured in vivo were erythema index: EI (using instrumental human skin blanching assay), transepidermal water loss (TEWL) and stratum corneum hydration (SCH). The vehicles based on cetearyl glucoside and cetearyl alcohol showed a complex colloidal structure of lamellar liquid-crystalline and lamellar gel-crystalline type, depending on oil polarity. Rheological profile of the vehicle was directly related to the in vitro profile of the HC permeation. In vivo results suggested that the vehicle with MG retarded the HC permeation, whereas less polar IPM and non-polar LP enhanced it. It is suggested that the enhancement is achieved either by a direct interaction with lipid lamellae of the SC or indirectly by improving skin hydration.

There were no adverse effects during in vivo study, which indicates a good safety profile of this alkylpolyglucoside surfactant.