A simple and selective high-performance liquid chromatography (HPLC) method using ultraviolet detection was developed for simultaneous determination of fusidic acid and betamethasone dipropionate in a cream formulation. A Supelcosil LC18 column was used for chromatographic separation. The mobile phase consisted of acetonitrile and 0.01 M disodium hydrogen orthophosphate (70:30, % v/v) adjusted to pH 6 with glacial acetic acid. Analysis was run at a flow rate of 1.0 mL/minute with the detector operating at 235 nm. The standard calibration curve was linear over a concentration range of 0.3 to 1.2 mg/mL for fusidic acid and 9.6 to 38.4 micrograms/mL for betamethasone dipropionate. The average recovery values for fusidic acid and betamethasone dipropionate were almost 100%. The within-run and between-run coefficient of variation and percent error values for the two drugs were all less than 2% and +/- 3%, respectively.
Compaction of controlled-release coated pellets into tablets is challenging because of the fusion of pellets and the rupturing of coated film. The difficulty in compaction intensifies with the use of extremely water-soluble drugs. Therefore, the present study was conducted to prepare and compact pellets containing pseudoephedrine hydrochloride as an extremely water-soluble model drug. The pellets were produced using an extrusion-spheronization technique. The drug-loaded pellets were coated to extend the drug release up to 12-h employing various polymers, and then they were compressed into tablets using microcrystalline cellulose Ceolus KG-801 as a novel tabletting excipient. The in vitro drug release studies of coated pellets and tablets were undertaken using the USP basket method in dissolution test apparatus I. The amount of drug released was analyzed at a wavelength of 215 nm. The combined coatings of hydroxypropyl methylcellulose and Kollicoat SR-30D yielded 12-h extended-release pellets with drug release independent of pH of dissolution medium following zero-order kinetics. The drug release from the tablets prepared using inert Celous KG-801 granules as tabletting excipient was found faster than that of coated pellets. However, a modification in drug release rate occurred with the incorporation of inert Ceolus KG-801 pellets. The drug dissolution profile from tablets containing 40% w/w each of coated pellets and inert granules along with 20% w/w inert pellets was found to be closely similar to that of coated pellets. Furthermore, the friability, tensile strength, and disintegration time of the tablets were within the USP specifications.
To investigate the interpolymer complexation between Carbopol 934P (CP) and various grades of polyvinylpyrrolidone (PVP) (K90, K32, C15, and VA/S-630).
Modified-release drug spheroids coated with an aqueous mixture of high-viscosity hydroxypropylmethylcellulose (HPMC) and sodium carboxymethylcellulose (NaCMC) were formulated. The preparation of core drug spheroids and the coating procedures were performed using the rotary processor and a bottom-spray fluidized bed, respectively. Dissolution studies indicated that incorporation of suitable additives, such as poly(vinylpyrrolidone) (PVP) and poly(ethylene glycol) 400 (PEG) improved the flexibility and integrity of the coat layer by retarding the drug release. An increase in coating levels applied generally retarded the release rate of the drug. However, the ratio of HPMC to NaCMC in the mixed, plasticized polymeric coat played a more dominant role in determining the dissolution T50% values. The optimal ratio of HPMC to NaCMC for prolonged drug release was found to be 3:1, whereas an increase in the amount of NaCMC in the mixed polymer coat only increased drug release. The synergistic viscosity effect of HPMC and NaCMC in retarding drug release rate was greater in distilled water than in dissolution media of pH 1 and 7.2. Cross-sectional view of the scanning electron micrograph showed that all of the coated spheroids exhibited a well-fused, continuous, and distinct layer of coating film. The drug release kinetics followed a biexponential first-order kinetic model.
This study examined the mechanical (hardness, compressibility, adhesiveness, and cohesiveness) and rheological (zero-rate viscosity and thixotropy) properties of polyethylene glycol (PEG) gels that contain different ratios of Carbopol 934P (CP) and polyvinylpyrrolidone K90 (PVP). Mechanical properties were examined using a texture analyzer (TA-XT2), and rheological properties were examined using a rheometer (Rheomat 115A). In addition, lidocaine release from gels was evaluated using a release apparatus simulating the buccal condition. The results indicated that an increase in CP concentration significantly increased gel compressibility, hardness, and adhesiveness, factors that affect ease of gel removal from container, ease of gel application onto mucosal membrane, and gel bioadhesion. However, CP concentration was negatively correlated with gel cohesiveness, a factor representing structural reformation. In contrast, PVP concentration was negatively correlated with gel hardness and compressibility, but positively correlated with gel cohesiveness. All PEG gels exhibited pseudoplastic flow with thixotropy, indicating a general loss of consistency with increased shearing stress. Drug release T50% was affected by the flow rate of the simulated saliva solution. A reduction in the flow rate caused a slower drug release and hence a higher T50% value. In addition, drug release was significantly reduced as the concentrations of CP and PVP increased because of the increase in zero-rate viscosity of the gels. Response surfaces and contour plots of the dependent variables further substantiated that various combinations of CP and PVP in the PEG gels offered a wide range of mechanical, rheological, and drug-release characteristics. A combination of CP and PVP with complementary physical properties resulted in a prolonged buccal drug delivery.
The purpose of this study was to design a 24-hour controlled porosity osmotic pump system that utilizes polyvinyl pyrrolidone (PVP) as an osmotic-suspending/release retarding agent of drugs.
A simple, rapid, specific and reliable UFLC coupled with ESI-MSMS assay method to simultaneously quantify sildenafil and N-desmethyl sildenafil, with loperamide as internal standard, was developed. Chromatographic separation was performed on a Thermo Scientific Accucore C18 column with an isocratic mobile phase composed of 0.1% v/v formic acid in purified water-methanol (20:80, v/v), at a flow rate of 0.3 mL/min. Sildenafil, N-desmethyl sildenafil and loperamide were detected with proton adducts at m/z 475.4 > 58.2, 461.3 > 85.2 and 477.0 > 266.1 in multiple reaction monitoring positive mode, respectively. Both analytes and internal standard were extracted by diethyl ether. The method was validated over a linear concentration range of 10-800 ng/mL for sildenafil and 10-600 ng/mL for N-desmethyl sildenafil with correlation coefficient (r(2) ) ≥0.9976 for sildenafil and (r(2) ) ≥0.9992 for N-desmethyl sildenafil. The method was precise, accurate and stable. The proposed method was applied to study the bioequivalence between a 100 mg dose of two pharmaceutical products: Viagra (original) and Edyfil (generic) products. AUC0-t , Cmax and Tmax were 2285.79 ng h/mL, 726.10 ng/mL and 0.94 h for Viagra and 2363.25 ng h/mL, 713.91 ng/mL and 0.83 hour for Edyfil. The 90% confidence interval of these parameters of this study fall within the regulatory range of 80-125%, hence they are considered as bioequivalent.
The effect of deprotenizing agents on recovery of donepezil hydrochloride in the development of a simple, rapid, selective and sensitive high performance liquid chromatography method for quantification of donepezil hydrochloride in human plasma was described. The deprotenizing agents were comprised of, perchloric acid, methanol, acetonitrile, chloroform and their mixtures. The chromatographic separation was carried out using reversed phase C18 column (Agilent Eclipse Plus C18) with UV detection at 268 nm. The mobile phase was comprised of 0.01 M potassium dihydrogen phosphate buffer, methanol and acetronitrile (50:30:20, v/v) adjusted to pH 2.7 with phosphoric acid (80%). A combination of perchloric acid and methanol gave a cleaner sample with a good recovery of donepezil hydrochloride of above 96%. The method showed intraday precision and accuracy in the range of 6.82% to 1.5% and 3.13% to 1.12% respectively, while interday precision and accuracy ranged between 1.06% to 4.71% and 13.01% to 6.43% respectively. The standard calibration curve was linear from 30ng/mL to 4000ng/mL, with a correlation coefficient of 0.9965±0.0034. The retention time of donepezil was 5.9 min with a run time of 7.0 min. The method can be applied to analyze large batch plasma samples in pharmacokinetic studies.
The objectives of this study were to develop a new deproteinization method to extract amoxicillin from human plasma and evaluate the inter-ethnic variation of amoxicillin pharmacokinetics in healthy Malay volunteers. A single-dose, randomized, fasting, two-period, two-treatment, two-sequence crossover, open-label bioequivalence study was conducted in 18 healthy Malay adult male volunteers, with one week washout period. The drug concentration in the sample was analyzed using high-performance liquid chromatography (UV-vis HPLC). The mean (standard deviation) pharmacokinetic parameter results of Moxilen® were: peak concentration (Cmax ), 6.72 (1.56) µg/mL; area under the concentration-time graph (AUC0-8 ), 17.79 (4.29) µg/mL h; AUC0-∞ , 18.84 (4.62) µg/mL h. Those of YSP Amoxicillin® capsule were: Cmax , 6.69 (1.44) µg/mL; AUC0-8 , 18.69 (3.78) µg/mL h; AUC00-∞ , 19.95 (3.81) µg/mL h. The 90% confidence intervals for the logarithmic transformed Cmax , AUC0-8 and AUC0-∞ of Moxilen® vs YSP Amoxicillin® capsule was between 0.80 and 1.25. Both Cmax and AUC met the predetermined criteria for assuming bioequivalence. Both formulations were well tolerated. The results showed significant inter-ethnicity variation in pharmacokinetics of amoxicillin. The Cmax and AUC of amoxicillin in Malay population were slightly lower compared with other populations.
A simple, rapid, specific and reliable high-performance liquid chromatographic assay of meloxicam in human plasma has been developed using a C18 reversed-phase analytical column. Reversed-phase chromatography was conducted using a mobile phase of 0.02 potassium dihydrogen phosphate (adjusted to pH 2.7 with phosphoric acid)-acetonitrile-triethylamine (35:65:0.05, v/v) with UV detection at 354 nm. The drug in human plasma was deproteinized using a combination of methanol and chloroform. This method is simple, rapid and consistent with a high recovery of meloxicam in human plasma ranging from 93.29 to 111.09%. Regression analysis for the calibration plot for plasma standards obtained for the drug concentrations between (25-4000) ng/mL indicated excellent linearity (r ≥ 0.9997). The proposed method was applied to study the bioequivalence between Mobic (original) and Melocam (generic) products. The study was conducted on using two tablets (4 × 7.5 mg) of each of the commercial product and the reference standard in a two-way open randomized crossover design involving 20 volunteers. Area under the concentration-time curve, peak concentration (C(max)) and time to reach C(max) were 72,868.61 ng h/mL, 2133.93 ng/mL and 4.06 h for Mobic, and 78,352.52 ng h/mL, 2525.18 ng/mL and 3.61 h for Melocam. Two C(max) were discovered in the pharmacokinetic profiles which confirm enterohepatic recirculation.
The effect of hydroxypropyl methylcellulose (HPMC) concentration on β-cyclodextrin (β-CD) solubilization of norfloxacin was examined. The solubility and dissolution of norfloxacin/β-CD and norfloxacin/β-CD/HPMC inclusion complexes were studied. The presence of β-CD increased significantly the solubility and dissolution of norfloxacin. The addition of HPMC until 5% (w/w) improved the solubilization of norfloxacin but further addition above 5% (w/w), decreased norfloxacin solubilization. Fourier transformed Infra-red (FTIR) showed that norfloxacin was successfully included into β-CD. Differential scanning calorimetry (DSC) showed that the norfloxacin endothermic peak shifted to a lower temperature with reduced intensity indicating the formation of inclusion complex. The addition of HPMC reduced further the intensity of norfloxacin endothermic peak. Most of the sharp and intense peaks of norfloxacin disappeared with the addition of HPMC. In conclusion, the concentration of hydrophilic polymer used to enhance β-CD solubilization of poorly soluble drugs is very critical.
An easy, fast and validated RV-HPLC method was invented to quantify donepezil hydrochloride in drug solution and orally disintegrating tablet. The separation was carried out using reversed phase C-18 column (Agilent Eclipse Plus C-18) with UV detection at 268 nm. Method optimization was tested using various composition of organic solvent. The mobile phase comprised of phosphate buffer (0.01M), methanol and acetonitrile (50:30:20, v/v) adjusted to pH 2.7 with phosphoric acid (80%) was found as the optimum mobile phase. The method showed intraday precision and accuracy in the range of 0.24% to -1.83% and -1.83% to 1.99% respectively, while interday precision and accuracy ranged between 1.41% to 1.81% and 0.11% to 1.90% respectively. The standard calibration curve was linear from 0.125 μg/mL to 16 μg/mL, with correlation coefficient of 0.9997±0.00016. The drug solution was stable under room temperature at least for 6 hours. System suitability studies were done. The average plate count was > 2000, tailing factor <1, and capacity factor of 3.30. The retention time was 5.6 min. The HPLC method was used to assay donepezil hydrochloride in tablet and dissolution study of in-house manufactured donepezil orally disintegrating tablet and original Aricept.
Microencapsulation of water-soluble drugs using coacervation-phase separation method is very challenging, as these drugs partitioned into the aqueous polymeric solution, resulting in poor drug entrapment. For evaluating the effect of ovalbumin on the microencapsulation of drugs with different solubility, pseudoephedrine HCl, verapamil HCl, propranolol HCl, paracetamol, and curcuminoid were used. In addition, drug mixtures comprising of paracetamol and pseudoephedrine HCl were also studied. The morphology, encapsulation efficiency, particle size, and in vitro release profile were investigated. The results showed that the solubility of the drug determined the ratio of ovalbumin to be used for successful microencapsulation. The optimum ratios of drug, ovalbumin, and gelatin for water-soluble (pseudoephedrine HCl, verapamil HCl, and propranolol HCl), sparingly water-soluble (paracetamol), and water-insoluble (curcuminoid) drugs were found to be 1:1:2, 2:3:5, and 1:3:4. As for the drug mixture, the optimum ratio of drug, ovalbumin, and gelatin was 2:3:5. Encapsulated particles prepared at the optimum ratios showed high yield, drug loading, entrapment efficiency, and sustained release profiles. The solubility of drug affected the particle size of the encapsulated particle. Highly soluble drugs resulted in smaller particle size. In conclusion, addition of ovalbumin circumvented the partitioning effect, leading to the successful microencapsulation of water-soluble drugs.
Obesity is one of the most important problems worldwide. Khat (Catha edulis), an evergreen shrub, is thought to reduce body-weight. Its effect is more prominent when khat leaves are chewed. Thus, anti-obesity effects of khat and its associated side effects may depend on the release rate of its active constituents. The present study aimed to investigate the effect of a selected low dose of dried-khat, extracted, formulated as controlled release delivery systems on the body weight (BW), food intake (FI), cholesterol (CS) and triglyceride (TG) levels in rats. Khat extract (KE) was microencapsulated (KE235) and formulated into a parenteral implant (InjKE235). The effects of KE, KE235 and InjKE235 on BW, FI, CS and TG in rats were investigated. The results showed that microcapsules sustained the khat alkaloid release with T50% 1.58 h for KE235 and 14.41 days for InjKE235. KE and KE235 caused maximum reduction in BW, FI, CS and TG during the first to third weeks but rebound gradually thereafter. On the contrary, InjKE235 exhibited a sustained reduction in BW, FI, CS and TG levels for 2 months. The T50% of KE, KE235 and InjKE235 correlated with the reduction in BW, CS and TG but not with FI. In conclusion, the subcutaneous injection and sustained release rate of khat extract play an important role in enhancing the anti-obesity effect in SD rats.:
The aim of this study was to develop a taste-masked oral disintegrating film (ODF) containing donepezil, with fast disintegration time and suitable mechanical strength, for the treatment of Alzheimer's disease. Hydroxypropyl methylcellulose, corn starch, polyethylene glycol, lactose monohydrate and crosspovidone served as the hydrophilic polymeric bases of the ODF. The uniformity, in vitro disintegration time, drug release and the folding endurance of the ODF were examined. The in vitro results showed that 80% of donepezil hydrochloride was released within 5 minutes with mean disintegration time of 44 seconds. The result of the film flexibility test showed that the number of folding time to crack the film was 40 times, an indication of sufficient mechanical property for patient use. A single-dose, fasting, four-period, eight-treatment, double-blind study involving 16 healthy adult volunteers was performed to evaluate the in situ disintegration time and palatability of ODF. Five parameters, namely taste, aftertaste, mouthfeel, ease of handling and acceptance were evaluated. The mean in situ disintegration time of ODF was 49 seconds. ODF containing 7 mg of sucralose were more superior than saccharin and aspartame in terms of taste, aftertaste, mouthfeel and acceptance. Furthermore, the ODF was stable for at least 6 months when stored at 40°C and 75% relative humidity.
Khat (Catha edulis) as well as garlic (Allium sativum) has a potential effect on reducing the lipid contents of blood. However, a mechanism by which garlic or khat reduces plasma lipids has not been fully investigated. This study aimed to investigate the direct action of khat and/or garlic (in vitro). The effects of extracted khat and/or garlic on human blood constituents (cholesterol and triglycerides) and on vegetable oil were investigated. The results showed that aqueous garlic extract was able to form an emulsion with oil but not khat extract. Even though, either khat or garlic extract has slight effect on reducing lipid contents of blood; a higher reduction was obtained when the extracts were added in combination. The mechanism of garlic on reducing lipids could be explained by its emulsifying property, while the mechanism of khat is by lipolysis. In conclusion, the synergistic effect of garlic and khat extracts opened an interesting area for further investigation on their roles in combating cardiovascular and obesity disorders.:
Khat (Catha edulis) is an evergreen tree/shrub that is thought to affect sexual motivation or libido. Its positive effect on sexual desire is more frequently observed in females than in males and occurs when khat is chewed. Thus, khat's effects on sexual behavior may depend on the release mode of its active constituent.
In this study, acidic deep eutectic solvents (DES) synthesized from various organic carboxylic acid hydrogen bond donors were applied to lignocellulosic oil palm empty fruit bunch (EFB) pretreatment. The influence of functional group types on acid and their molar ratios with hydrogen bond acceptor on lignin extraction were evaluated. The result showed presence of hydroxyl group and short alkyl chain enhanced biomass fractionation and lignin extraction. Choline chloride:lactic acid (CC-LA) with the ratio of 1:15 and choline chloride:formic acid (CC-FA) with 1:2 ratio extracted more than 60 wt% of lignin. CC-LA DES-extracted lignin (DEEL) exhibited comparable reactivity with technical and commercial lignin based on its phenolic hydroxyl content (3.33-3.72 mmol/glignin). Also, the DES-pretreated EFB comprised of enriched glucan content after biopolymer fractionation. Both DES-pretreated EFB and DEEL can be potential feedstock for subsequent conversion processes. This study presented DES as an effective and facile pretreatment method for reactive lignin extraction.
The potential of using poly-(ethylene oxide)-block-distearoyl phosphatidyl-ethanolamine (mPEG-DSPE) polymer to prepare BDP-loaded micelles with high entrapment efficiency and mass median aerodynamic diameter of less than 5 microm demonstrating sustained release properties was evaluated. The result showed that lyophilized BDP-loaded polymeric micelles with entrapment efficiency of more than 96% could be achieved. Entrapment efficiency was affected by both the drug to polymer molar ratio and the amount of drug used. Investigation using FTIR and DSC confirmed that there was no chemical or physical interaction and the drug was molecularly dispersed within the micelles. TEM images showed that the drug-loaded polymeric micelles were spherical in shape with multivesicular morphology. Further analysis by photon correlation spectroscopy indicated that the particle size of the BDP-loaded micelles was about 22 nm in size. In vitro drug release showed a promising sustained release profile over six days following the Higuchi model. The mass median aerodynamic diameter and fine particle fraction were suitable for pulmonary delivery. Moreover, the small amount of deposited drug in the induction port (throat deposition) suggested possible reduction in incidence of oropharyngeal candidiasis, a side effect normally associated with inhaled corticosteroids therapy. The high encapsulation efficiency, comparable inhalation properties, sustained release behavior together with biocompatibility nature of the polymer support the potential of BDP-loaded polymeric micelles as a versatile delivery system to be used in the treatment of asthma and chronic obstructive pulmonary disease.
Since the introduction of deep eutectic solvent (DES) in biomass processing field, the efficiency of DES in lignocellulosic biopolymer model compounds' (cellulose, hemicellulose and lignin) solubilisation and conversion was widely recognized. Nevertheless, DES's potential for biorefinery application can be reflected more accurately through their performance in raw lignocellulosic biomass processing rather than model compound conversion. Therefore, this review examines the studies on raw lignocellulosic biomass fractionation using DES and the subsequent conversion of DES-fractionated products into bio-based products. The review stresses on three key parts: performance of varying types of DESs and pretreatment schemes for biopolymer fractionation, properties and conversion of fractionated saccharides as well as DES-extracted lignin. The prospects and challenges of DES implementation in biomass processing will also be discussed. This review provides a front-to-end view on the DES's performance, starting from pretreatment to DES-fractionated products conversion, which would be helpful in devising a comprehensive biomass utilization process.