Nanoethosomes mediated transdermal delivery of vinpocetine for management of Alzheimer's disease.

AIM: To develop and statistically optimize nanoethosomal formulation for transdermal delivery of vinpocetine as an anti-Alzheimer's drug. MATERIALS AND METHODS: Box-Behnken experimental design was applied for optimization of nanoethosomes. The independent variables were phospholipid (X1), Tween 80 (X2) and Ethanol (X3) while entrapment efficiency (Y1), particle sizes (Y2), elasticity (Y3) and flux (Y4) were the dependent variables. RESULTS AND CONCLUSION: Optimized nanoethosomal vinpocetine formulation with mean particle size 50.57 ± 26.11 nm showed 97.51 ± 0.86% entrapment efficiency, achieved mean transdermal flux 925.60 ± 39.80 µg/cm2/h and elasticity of 86.61 ± 2.88. Ex-vivo study of nanoethosomal formulation showed a significant increase flux and entrapment efficiency compared with control vinpocetine solution. Our results suggest that nanoethosome is an efficient carrier for transdermal delivery of vinpocetine as compared to its oral form.

Formulation, development and optimization of raloxifene-loaded chitosan nanoparticles for treatment of osteoporosis.

CONTEXT: Osteoporosis (OP) is a disease of skeletal system and is associated with fragility fracture at the hip, spine and wrist. Various drugs have been used to treat OP. One of them is raloxifene hydrochloride (RLX), a second-generation selective estrogen receptor modulator (SERM) approved by the USFDA. RLX possesses only 2% absolute bioavailability (BA) by oral route due to its extensive first-pass metabolism. OBJECTIVE: The purpose of the current research work was to develop and evaluate RLX-loaded chitosan nanoparticles (CS-NPs) for treatment of OP with enhanced BA. MATERIALS AND METHODS: The RLX-loaded CS-NPs were prepared by gelation of CS with tripolyphosphate (TPP) by ionic cross-linking. Formulation was optimized and in vitro drug release and in vivo study were performed. RESULTS AND DISCUSSIONS: CS-NPs were formed by the ionic gelation method. The particle size, entrapment efficiency and loading efficiency varied from 216.65 to 1890 nm, 32.84 to 97.78% and 23.89 to 62.46%, respectively. Release kinetics showed diffusion-controlled and Fickian release pattern. In vivo study indicated higher plasma drug concentration with NPs administered intranasally as compared to drug suspension administered through oral route (p < 0.05). A significantly higher drug concentration in plasma was achieved in 10 min after nasal administration with respect to oral administration. CONCLUSION: The results suggest that RLX-loaded CS-NPs have better BA and would be a promising approach for intranasal (i.n.) delivery of RLX for the treatment of OP.

Design, characterization, and evaluation of intranasal delivery of ropinirole-loaded mucoadhesive nanoparticles for brain targeting.

CONTEXT: Parkinson disease (PD) is a common, progressive neurodegenerative disorder, characterized by marked depletion of striatal dopamine and degeneration of dopaminergic neurons in the substantia nigra. OBJECTIVE: The purpose of the present study was to investigate the possibility of targeting an anti-Parkinson's drug ropinirole (RH) to the brain using polymeric nanoparticles. MATERIALS AND METHODS: Ropinirole hydrochloride (RH)-loaded chitosan nanoparticles (CSNPs) were prepared by an ionic gelation method. The RH-CSNPs were characterized for particle size, polydispersity index (PDI), zeta potential, loading capacity, entrapment efficiency in vitro release study, and in vivo distribution after intranasal administration. RESULTS AND DISCUSSION: The RH-CSNPs showed sustained release profiles for up to 18 h. The RH concentrations (% Radioactivity/g) in the brain following intranasal administration (i.n.) of RH-CSNPs were found to be significantly higher at all the time points compared with RH solution. The concentration of RH was highest in the liver (7.210 ± 0.52), followed by kidneys (6.862 ± 0.62), intestine (4.862 ± 0.45), and lungs (4.640 ± 0.92) in rats following i.n. administration of RH-CSNPs. Gamma scintigraphy imaging in rats was performed to ascertain the localization of drug in the brain following intranasal administration of formulations. The brain/blood ratios obtained (0.251 ± 0.09 and 0.386 ± 0.57 of RH (i.n.) and RH-CSNPs (i.n.), respectively) at 0.5 h are indicative of direct nose to brain transport, bypassing the blood-brain barrier (BBB). CONCLUSION: The novel formulation showed the superiority of nose to brain delivery of RH using mucoadhesive nanoparticles compared with other delivery routes reported earlier.

Formulation of extended release cefpodoxime proxetil chitosan-alginate beads using quality by design approach.

The purpose of this work was to develop and characterize chitosan-alginate beads for the extended delivery of cefpodoxime proxetil (CFP), to understand the impact of formulation and process parameters on the critical quality attributes (CQAs) using a quality-by-design approach. For this, a study was performed with various formulation and process parameters to determine their impact on CQAs of beads, which were determined to be time for 80% of the drug released (T80%), particle size, and encapsulation efficiency. The beads of CFP were optimized using a three-factor, three-level Box-Behnken design. A formulation comprising of 4.38% (w/v) alginate, 1.39% (w/v) chitosan and 6.82% (w/v) calcium chloride was found to fulfill requisites of an optimum formulation. In vitro release studies showed that the drug is released from the optimized formulation over a period of 24h in a sustained release manner, primarily by non-Fickian diffusion. The optimized formulation was characterized by DSC, FTIR, XRD and SEM analysis. Antimicrobial studies revealed that the release of the drug over 24h periods was above the minimum concentration required for inhibition of microbial growth. This research highlights the level of understanding that can be accomplished through a well designed study based on the approach of QbD.

Pharmacoscintigraphic evaluation of potential of lipid nanocarriers for nose-to-brain delivery of antidepressant drug.

Efficacy of antidepressants relies upon their continued presence at the site of action (brain) over a prolonged period of time. The BBB restricts the access of antidepressants to the brain on oral as well as intravenous administration. Direct delivery (by-passing the BBB) of antidepressant drugs can increase the CSF concentration with concomitant reduction in dose and side effects. Intranasal administration of nanostructured lipid carriers (NLC) containing antidepressant drug circumvent the BBB and maintain the prolonged release at the site of action. The aim of the present study was to evaluate the enhancement in brain uptake of NLC containing duloxetine (DLX) after intranasal administration. Duloxetine loaded NLC (DLX-NLC) was evaluated pharmacoscintigraphically for drug targeting potential (DTP), drug targeting efficiency (DTE) and biodistribution studies in different organs including brain. The radiolabeling efficiency of DLX and DLX-NLC was found to be 98.41 ± 0.96 and 98.87 ± 0.82 after 30 min, respectively. The biodistribution studies exhibited higher percentage of radioactivity/g for DLX-NLC formulations in brain as compared with the DLX. The higher DTP (86.80%) and DTE (757.74%) suggested that DLX-NLC formulation has a better brain targeting efficiency than DLX solution (DTP=65.12%; DTE=287.34%) when administered intranasally. Moreover, the intranasal administration exhibited about 8-times higher concentration of DLX in brain when compared with the intravenous administration of DLX solution. The intranasal NLC containing DLX can be employed as an effective method for the treatment of depression.

Donepezil nanosuspension intended for nose to brain targeting: In vitro and in vivo safety evaluation.

The present study was to develop donepezil loaded nanosuspension for direct olfactory administration which reaches the brain and determining safety profile in Sprague-Dawley rats. Nanosuspension was prepared by ionic-crosslinking method. The developed nanosuspension was intranasally instilled into the nostrils of rats with the help of cannula (size 18/20) so that drug reached into the brain directly via nose to brain pathway. The nanosuspension had an average size of 150-200nm with a polydispersity index of 0.341. The donepezil concentration was estimated in the brain homogenate using HPLC method. The Cmax showed concentration of donepezil in brain and plasma as 7.2±0.86 and 82.8±5.42ng/ml, respectively, for drug suspension and concentration of donepezil in brain and plasma as 147.54±25.08 and 183.451±13.45ng/ml, respectively, for nanosuspension at same dose of 0.5mg/ml when administered intranasally (p<0.05). The in vivo safety evaluation studies showed that no mortality, hematological changes, body weight variations and toxicity in animals was observed, when nanosuspension was administered in different doses as compared to control group (normal saline). Donepezil loaded chitosan nanosuspension is a potential new delivery system for treatment of Alzheimer's disease, when transported via olfactory nasal pathway to the brain.

Preparation, characterization, in vivo biodistribution and pharmacokinetic studies of donepezil-loaded PLGA nanoparticles for brain targeting.

OBJECTIVE: Alzheimer's disease (AD) is a progressive neurodegenerative disorder manifested by cognitive, memory deterioration and variety of neuropsychiatric symptoms. Donepezil is a reversible cholinesterase inhibitor used for the treatment of AD. The purpose of this work is to prepare a nanoparticulate drug delivery system of donepezil using poly(lactic-co-glycolic acid) (PLGA) for sustained release and efficient brain targeting. MATERIALS AND METHODS: PLGA nanoparticles (NPs) were prepared by the solvent emulsification diffusion-evaporation technique and characterized for particle size, particle-size distribution, zeta potential, entrapment efficiency, drug loading and interaction studies and in vivo studies using gamma scintigraphy techniques. RESULTS AND DISCUSSION: The size of drug-loaded NPs (drug polymer ratio 1:1) was found to be 89.67 ± 6.43 nm. The TEM and SEM images of the formulation suggested that particle size was within 20-100 nm and spherical in shape, smooth morphology and coating of Tween-80 on the NPs was clearly observed. The release behavior of donepezil exhibited a biphasic pattern characterized by an initial burst release followed by a slower and continuous sustained release. The biodistribution studies of donepezil-loaded PLGA NPs and drug solution via intravenous route revealed higher percentage of radioactivity per gram in the brain for the nanoparticulate formulation as compared with the drug solution (p < 0.05). CONCLUSION: The high concentrations of donepezil uptake in brain due to coated NPs may help in a significant improvement for treating AD. But further, more extensive clinical studies are needed to check and confirm the efficacy of the prepared drug delivery system.

Lipid drug conjugate nanoparticle as a novel lipid nanocarrier for the oral delivery of decitabine: ex vivo gut permeation studies.

The purpose of this study was to develop lipid drug conjugate (LDC) nanoparticles of decitabine (DCB) using stearic acid as a lipid to increase the permeability of the drug along with its protection from chemical degradation. The LDC was prepared by salt formation of DCB with stearic acid and followed by cold homogenization technique to produce the LDC nanoparticles. The role of key independent variables influencing on dependent variables were determined by using a Box-Behnken design. The optimized batch revealed spherical morphology under TEM analysis with particle size of 202.6 ± 1.65 nm and 0.334 ± 0.987 PDI. The zeta potential and %EE were found to be -33.6 ± 0.845 mV and 68.89% ± 0.59 respectively. Lyophilized powder showed the crystalline structure under DSC analysis. In vitro release studies showed the initial burst release followed by a sustained release up to 24 h in PBS pH 7.4 and the data were further studied using release kinetic models which revealed the first-order model as a best-fitting model. Ex vivo gut permeation studies proved that the formulation containing lipid and surfactants has a higher permeability than the plain drug solution with nearly fourfold increase in the apparent permeability coefficients. Finally, LDC nanoparticles prepared by using stearic acid as a lipid and surfactants as Tween 80, Poloxamer 188, and Labrasol in equal ratio possess high potential for the oral delivery of hydrophilic drugs.

Intranasal infusion of nanostructured lipid carriers (NLC) containing CNS acting drug and estimation in brain and blood.

The present study was aimed to evaluate the nanostrucured lipid carriers (NLC) containing duloxetine (DLX-NLC) for intranasal infusion through the nasal cavity of rat. The in vivo nasal infusion studies were performed using Wistar rats and the amount of DLX permeated and its amount in brain and blood was estimated. The effects on absorption rate and type of drug delivery systems (nanocarriers and drug solution) for nose to brain/blood permeation were assessed. DLX was found to be permeated from the nasal cavity into the body of rat and the permeated amount was found to be more in case of DLX-NLC. Approximately 2.5-times better permeation was exhibited by DLX-NLC than DLX-solution. Appreciable amount of DLX was estimated in blood and brain and the estimated amount was higher in case of DLX-NLC. Thus the administration of NLC containing DLX through intranasal route was found to be potential method for the delivery of DLX for the treatment of depression.

Intranasal administration of nanostructured lipid carriers containing CNS acting drug: pharmacodynamic studies and estimation in blood and brain.

The present study was aimed to investigate and compare the efficacy of duloxetine (DLX) loaded nanostructured lipid carriers (NLC) with DLX solution pharmacodynamically following intranasal administration. The study was further conducted to estimate DLX concentration in brain and blood. DLX was administered to albino Wistar rats either intranasally or orally in solution form (DLX solution) or encapsulated in NLC (DLX-NLC). These were evaluated in-vivo for pharmacodynamic studies for depression by forced swimming test and locomotor activity test. Intranasal DLX-NLC treatment exhibited improved behavioural analysis results (swimming, climbing, and immobility) than the DLX solution after 24 h of study. Furthermore, DLX-NLC significantly increased the total swimming and climbing time when compared with control and significantly reduced the immobility period. The intranasal DLX-NLC demonstrated improved locomotor activity when compared with DLX solution. Amount of DLX was quantified in blood and brain after the forced swimming test. The intranasal DLX-NLC demonstrated higher concentration in brain compared with DLX solution. Thus, intranasal DLX-NLC was found to be a promising formulation for the treatment of depression.

Development and validation of a stability-indicating method for determination of free sterols in the Asian medicinal leech Hirudo manillensis.

A rapid, simple, sensitive, selective, precise and robust thin-layer chromatography densitometric method for the determination of free sterols in leech was developed and validated on silica gel layer using carbon tetrachloride-methanol-formic acid (9.5:1.5:0.55, v/v/v). Spectrodensitometric scanning was carried using a Camag TLC scanner III at 366 nm after spraying 2% methanolic sulphuric acid, which gave compact spots for cholesterol (R(F) = 0.35 ± 0.02). The regression analysis data for calibration plot implied a good linear relationship (r(2) = 0.99958) between response and concentration over the range 100-600 ng per spot with respect to peak area. The limits of detection and quantification were found to be 13.8 ± 0.51 and 45.01 ± 1.29 ng per spot, respectively. Validation was in accordance to the International Conference on Harmonization guidelines. Cholesterol was subjected to forced stress conditions of oxidation, hydrolysis and heat. Degradation products resulting from the forced stress did not interfere with detection because the degradant peaks were well separated from the cholesterol peak. The densitometric method can be regarded as stability-indicating and can be used for quality control assay of cholesterol in leech extract.

Reduced bioavailability of tamoxifen and its metabolite 4-hydroxytamoxifen after oral administration with biochanin A (an isoflavone) in rats.

The aim of this study was to investigate the effect of biochanin A (BCA) on the pharmacokinetics of tamoxifen, a substrate of P-glycoprotein (P-gp) and cytochrome 3A (CYP3A), in female rats. The tamoxifen was administered orally (10 mg/kg) without or with oral BCA (100 mg/kg) in female rats. As BCA is an inhibitor of CYP 3A and P-gp it was expected to increase the bioavailability of tamoxifen, a known substrate of CYP3A4/Pgp. Surprisingly, compared with the control group (treated with tamoxifen alone), BCA pretreated animals showed significantly (p < 0.05) decreased area under the plasma concentration-time curve from time zero to time infinity (AUC(0-∞)) and peak tamoxifen concentrations (C(max)). Consequently, the relative bioavailability (RB%) of tamoxifen co-administered with BCA was remarkably decreased compared with the control group. The AUC(0-∞) and C(max) of 4-hydroxytamoxifen in BCA pretreated rats were also significantly (p < 0.05) lower than those from the control group. However, there were no apparent changes in the metabolite ratio (MR; AUC(0-∞) of 4-hydroxytamoxifen to tamoxifen) by co-administration of BCA. If the results of this study are further confirmed by clinical trials, tamoxifen dosages should be adjusted to avoid potential drug interaction when tamoxifen is used clinically in combination with BCA and BCA-containing dietary supplements.

Liquid chromatography-mass spectrometry method for the quantification of tamoxifen and its metabolite 4-hydroxytamoxifen in rat plasma: application to interaction study with biochanin A (an isoflavone).

Tamoxifen is the agent of choice for the treatment of estrogen receptor-positive breast cancer. Tamoxifen is a substrate of P-glycoprotein (P-gp) and microsomal cytochrome P450 (CYP) 3A, and biochanin A (BCA) is an inhibitor of P-gp and CYP3A. Hence, it could be expected that BCA would affect the pharmacokinetics of tamoxifen. In the present study we have developed and validated a simple, sensitive and specific LC-ESI-MS/MS method for the simultaneous quantification of tamoxifen and its metabolite 4-hydroxytamoxifen with 100 µL rat plasma using centchroman as an internal standard (IS). Tamoxifen, 4-hydroxytamoxifen and IS were separated on a Supelco Discovery C18 (4.6 mm × 50 mm, 5.0 µm) column under isocratic condition using 0.0 1M ammonium acetate (pH 4.5):acetonitrile (10:90, v/v) as a mobile phase. The mobile phase was delivered at a flow rate of 0.8 mL/min. The method was proved to be accurate and precise at linearity range of 0.78-200 ng/mL with a correlation coefficient (r) of ≥ 0.996. The intra- and inter-day assay precision ranged from 1.89 to 8.54% and 3.97 to 10.26%, respectively; and intra- and inter-day assay accuracy was between 87.63 and 109.06% and 96 and 103.89%, respectively for both the analytes. The method was successfully applied to study the effect of oral co-administration of BCA (an isoflavone) on the pharmacokinetics of tamoxifen and 4-hydroxytamoxifen in female rats. The coadministration of BCA caused no significant changes in the pharmacokinetics of tamoxifen and 4-hydroxytamoxifen. However, the peak plasma concentration (C(max)) of 4-hydroxytamoxifen in BCA pretreated rats was significantly (P<0.05) lower than those from control group.

Reassessing bioavailability of silymarin.

Silymarin, a flavonolignan derived from Silybum marianum, possesses diverse pharmacological activities, including hepatoprotective, antioxidant, anti-inflammatory, anticancer, and cardioprotective. Although clinical trials have shown silymarin is safe at high doses (>1500 mg/day) in humans, the pharmacokinetic studies over the past three decades related to absorption, distribution, metabolism, and excretion of silymarin have revealed poor absorption, rapid metabolism, and ultimately poor oral bioavailability. For optimum silymarin bioavailability, issues of solubility, permeability, metabolism, and excretion must be addressed. An array of methods have been described in recent years that can improve its bioavailability, including complexation with ß-cyclodextrins, solid dispersion method, formation of microparticles and nanoparticles, self-microemulsifying drug delivery systems, micelles, liposomes, and phytosomes. This article critically reviews the recent published literature on various techniques for increasing the bioavailability of silymarin.

Nanocarrier for the enhanced bioavailability of a cardiovascular agent: in vitro, pharmacodynamic, pharmacokinetic and stability assessment.

The goals of the current study were to develop and characterize a nanoemulsion of ezetimibe, evaluate its stability, lipid lowering and pharmacokinetic profile. Solubility of the drug was estimated in various oils and surfactants. Existence of nanoemulsion region was confirmed by plotting phase diagrams. Various thermodynamic stability and dispersibility tests were performed on the formulations chosen from phase diagram. Percentage transmittance, refractive index, viscosity, droplet size and zeta potential of the optimized formulations were determined. Dialysis bag method was employed to study the release rate. The formulation selected for bioavailability estimation contained Capryol 90 (10%, v/v), Crempophor EL (11.25%, v/v), Transcutol(®) P (33.75%, v/v), and double distilled water (45%, v/v). The release rate from the nanoemulsion was highly significant (p<0.001) in contrast to the drug suspension. The level of total cholesterol in the group receiving nanoemulsion CF1 was found to be highly significant (p<0.001) in comparison to the group receiving drug suspension. Bioavailability studies in rats revealed superior absorption of ezetimibe from nanoemulsion as compared to the marketed formulation and drug suspension. The shelf life of the nanoemulsion was estimated to be 18.53 months. The present study corroborated nanoemulsion to be a promising choice to improve the bioavailability of ezetimibe.

High-throughput quantification of isoflavones, biochanin A and genistein, and their conjugates in female rat plasma using LC-ESI-MS/MS: Application in pharmacokinetic study.

Isoflavones containing foods and dietary supplements are widely consumed for putative health benefits (e.g. cancer chemoprevention, beneficial effects on serum lipids associated with cardiovascular health, reduction of osteoporosis, relief of menopausal symptoms). This paper describes the development and validation of a sensitive high throughput LC-ESI-MS/MS method for quantifying biochanin A (BCA) and genistein (GEN), and their conjugates in rat plasma. The analytes were separated on a Supelco Discovery C18 (4.6×50 mm, 5.0 µm) column under isocratic condition using acetonitrile/methanol (50:50, v/v) and 0.1% acetic acid in the ratio of 90:10 v/v as a mobile phase. The intra- and inter-day assay precision ranged from 2.66 to 8.34% and 4.40 to 8.10% (RSD %), respectively, and intra- and inter-day assay accuracy was between 90.67-109.25% and 95.86-106.32%, respectively, for both the analytes. The lowest quantitation limit for BCA and GEN was 0.5 ng/mL in 0.1 mL of rat plasma. The method was successfully applied to the estimation of BCA, GEN and their conjugates in rat plasma following oral administration of BCA. Circulating conjugates (glucuronides/sulfates) of BCA and GEN were quantified using enzymatic hydrolysis of plasma samples. The levels of isoflavones glucuronides/sulfates were found to be much greater than the corresponding aglycones.

Solid dispersion as an approach for bioavailability enhancement of poorly water-soluble drug ritonavir.

Ritonavir is an antiretroviral drug characterized by low solubility and high permeability which corresponds to BCS class II drug. The purpose of the study was to develop solid dispersion by different methods and investigate them for in vitro and in vivo performance for enhancing dissolution and bioavailability, respectively. Since the drug possesses food-related absorption, the effect of biorelevant media (FaSSIF and FeSSIF state) on dissolution behavior was also studied. The solid dispersion was prepared using Gelucire as carrier in 1:4 ratio by different methods and were characterized for differential scanning calorimetry (DSC), X-ray diffractometry, scanning electron microscopy, and FT-IR. Oral bioavailability of 10 mg of ritonavir in solid dispersion prepared by solvent evaporation (SE1) and melt method (MM1) was compared with pure drug after oral administration of solid dispersion and pure drug to Albino Wistar rats of either sex. The results suggested formation of eutectic solid dispersion. In vitro dissolution studies was performed in 0.1 N HCl and biorelevant media showed enhanced dissolution rate as compared to pure drug in both FeSSIF media and 0.1 N HCl. The apparent rate of absorption of ritonavir from SE1 (C(max) 20221.37 ng/ml, t(max) 0.5 h) was higher than that of MM1 (C(max) 2,462.2, t(max) 1 h) and pure drug (C(max) 1,354.8 ng/ml, t(max) 0.5 h). On the basis of the result obtained, it was concluded that solid dispersion is a good approach to enhance solubility and bioavailability of poorly water-soluble ritonavir.

Potential of nanoparticulate drug delivery systems by intranasal administration.

Due to number of problems related with oral, parenteral, rectal and other routes of drug administration, the interest of pharmaceutical scientists has increased towards exploring the possibilities of intranasal delivery of various drugs. Nasal drug delivery system is commonly known for the treatment of local ailments like cold, cough, rhinitis, etc. Efforts have been made to deliver various drugs, especially peptides and proteins, through nasal route for systemic use; utilizing the principles and concepts of various nanoparticulate drug delivery systems using various polymers and absorption promoters. The incorporation of drugs into nanoparticles might be a promising approach, since colloidal formulations have been shown to protect them from the degrading milieu in the nasal cavity and facilitate their transport across the mucosal barriers. The use of nanoparticles for vaccine delivery provides beneficial effect, by achieving good immune responses. This could be due to the fact that small particles can be transported preferentially by the lymphoid tissue of the nasal cavity (NALT). The brain gets benefited through the intranasal delivery as direct olfactory transport bypasses the blood brain barrier and nanoparticles are taken up and conveyed along cell processes of olfactory neurons through the cribriform plate to synaptic junctions with neurons of the olfactory bulb. The intranasal delivery is aimed at optimizing drug bioavailability for systemic drugs, as absorption decreases with increasing molecular weight, and for drugs, which are susceptible to enzymatic degradation such as proteins and polypeptides. This review discusses the potential benefits of using nanoparticles for nasal delivery of drugs and vaccines for brain, systemic and topical delivery. The article aims at giving an insight into nasal cavity, consideration of factors affecting and strategies to improve drug absorption through nasal route, pharmaceutical dosage forms and delivery systems with examples of some patents for intranasal delivery, its advantages and limitations.

Patented bioavailability enhancement techniques of silymarin.

The present article dwells in reviewing critically the patents published mainly on the new emerging trends and techniques for increasing the bioavailability of silymarin, the polyphenolic fraction obtained from the seeds of Silybum marianum. The use of this herb for treating various ailments like hepatitis, cirrhosis, jaundice, mushroom and toxin poisoning is well known. But the potential use of this herbal drug is limited due to the poor absorption and poor bioavailability after oral administration The belief that the natural medicines are much safer than synthetic drugs, has gained popularity in recent years and led to tremendous growth of phytopharmaceutical usage and thus the need of improving the bioavailability by various means like complexation, derivatization, solubilization, targeted delivery, controlled delivery and many other miscellaneous techniques.

Novel nanoemulsion for minimizing variations in bioavailability of ezetimibe.

The objectives of the present study were to develop an optimal nanoemulsion of ezetimibe and evaluate its stability, lipid lowering and pharmacokinetic potential. Solubility of ezetimibe was determined in various vehicles. Pseudoternary phase diagrams were constructed to determine the existence of nanoemulsion region. Formulations were selected from the oil/water nanoemulsion region and subjected to various thermodynamic stability and dispersibility tests. Release rate of optimized formulations was determined using in vitro dissolution test. The formulation used for evaluation contained Capryol 90 (10% v/v), Tween 80 (15% v/v), Transcutol P (30% v/v), double distilled water (45% v/v). The release of drug from the nanoemulsion was highly significant (P <0.001) when compared to the drug suspension. The value of total cholesterol in the group administered with the formulation TF1 was highly significant (P <0.001) with respect to the group administered with the suspension of the drug. The plasma concentration time profile of ezetimibe from nanoemulsion represented greater improvement of drug absorption than the marketed formulation and drug suspension. The shelf life of the nanoemulsion was found to be 5.94 years at room temperature. The present study established nanoemulsion to be a possible alternative for minimizing variation in bioavailability of ezetimibe.