In-vivo Pharmacokinetic Study Research Articles

Novel pH-sensitive interpenetrated network polyspheres of polyacrylamide-g-locust bean gum and sodium alginate for intestinal targeting of ketoprofen: In vitro and in vivo evaluation

In this report, novel pH-sensitive interpenetrated network (IPN) polyspheres were developed utilizing polyacrylamide-g-locust bean gum (PAAm-g-LBG) in combination with sodium alginate (SA) to achieve intestinal targeted delivery of ketoprofen. PAAm-g-LBG was synthesized under microwave irradiation wherein ceric ammonium nitrate was used as reaction initiator and then conversion of PAAm-g-LBG as pH-sensitive copolymer was carried out by alkaline hydrolysis. The PAAm-g-LBG copolymer was characterized through 1H-NMR, FTIR and elemental analysis. The IPN polyspheres exhibited pH-depended swelling or de-swelling with the alteration of surrounding pH. The in-vitro release of drug from IPN polyspheres was found to be higher (≈ 90%) in phosphate buffer of pH 7.4 in comparison with that in pH 1.2 buffer (10.6%). The in-vivo pharmacokinetic, anti-inflammatory screening and stomach histopathology studies performed on Wistar rats revealed pH sensitivity of IPN polyspheres where ketoprofen was successfully targeted to small intestine resulting in reduced side effects of ketoprofen like ulcer formation, erosion of gastric mucosa and hemorrhages.

Absorption enhancement effect of piperine and chitosan on ganciclovir sol-id lipid nanoparticles: formulation, optimization and invivo pharmacoki-netics

The purpose of the present study was to formulate Solid Lipid Nanoparticles (SLNs) of Ganciclovir (GCV) in combination with Chitosan and Piperine for absorption enhancement effect. GCV loaded SLNs were prepared by hot homogenization method, optimized and characterized. Formulated SLNs were incorporated with absorption enhancers and characterized for invitro absorption (with chicken intestine), histopathological and invivo pharmacokinetic studies. Invitro absorption studies revealed that the permeability coefficient of the prepared formulation is more when compared to the pure drug, so the permeability is more for prepared formulation. In vivo pharmacokinetic study showed a significant increase in the Cmax, AUC, biological half-life and decrease in elimination rate constant for prepared formulation compared to pure drug. Histopathological studies also showed mild reversible damage of epithelial cells with Chitosan which indicates the safety and efficacy of the formulation. Thus, GCV loaded SLNs prepared with Chitosan can be clinically promising for enhancing the oral, intestinal absorption of the said BCS Class-III drug.

Design and evaluation of novel inhalable sildenafil citrate spray-dried microparticles for pulmonary arterial hypertension

Pulmonary delivery of vasodilators is a promising alternative for the intravenous and oral treatment of pulmonary arterial hypertension (PAH). The aim of this study was to design and evaluate hydrogel microparticles as a carrier for sustained pulmonary delivery of sildenafil citrate. Spray dried hydrogel microparticles containing biodegradable sodium carboxymethyl cellulose, sodium alginate, and sodium hyaluronate polymers at variable concentrations were prepared. A design of experiment using the “Extreme Vertices Mixture” design was executed. The design was used to study the influence of polymer concentration and their interactions on the physicochemical properties of the formulations in terms of particle size, particle size distribution, product yield, entrapment efficiency, and in-vitro drug release. Selected formulations were also evaluated for swelling, biodegradation, moisture content, in-vitro aerodynamic performance, and cytotoxicity. In addition, a lung deposition and pharmacokinetic study was conducted in rats to study drug accumulation in lungs and blood after intratracheal administration of the spray dried inhalable hydrogel microparticles in comparison to orally administered Viagra®. The results demonstrated that formulated microparticles had a mean geometric particle size between 2 and 5 μm, entrapment efficiency of >80%, and yield ranging between 47 and 66% w/w. The in-vitro drug release profiles showed a sustained drug release of sildenafil citrate for over 24 h. The statistical design showed a significant influence of the microparticulate composition on the physicochemical properties. Furthermore, selected formulations were evaluated for their aerodynamic properties. The aerodynamic properties included fine particle fraction ranging between 24 and 30%, dose recovery percent of 68–8 5%, and average mass median aerodynamic diameter of 4.6–4.8 μm. The in-vivo pharmacokinetic study showed that inhaled spray dried hydrogel microparticles (M6) formulation had significantly higher lung/blood Cmax, AUC, extended half-life, and mean residence time in comparison to orally administered sildenafil citrate of the same dose. In conclusion, the formulated drug-loaded spray dried hydrogel microparticles showed promising in-vitro and in-vivo results for the pulmonary delivery of sildenafil citrate. The spray dried hydrogel microparticles formulation can be considered as a potential alternative of oral sildenafil citrate for treatment of PAH.

Floating Osmotic Drug Delivery System: A Review

Floating Osmotic Drug Delivery System (FODDS) is a controlled oral drug delivery system which comes under the category of Gastroretentive Drug Delivery (GRDDS). It is based upon the osmotically controlled release mechanism which offers a sustained therapeutic action while reducing the side effects. Various drugs with a shorter half-life and a small absorption window get highly benefited By FODDS. FODDS also finds a unique place among the other GRDDS by surpassing their performance. FODDS incorporates a variety of ingredients such as osmotic agents, semi permeable substance, gas generating Agent and a gel forming agent. The preparation of the system involves techniques like direct compression and coating process. Characterisation studies like in-vitro dissolution study, in-vivo radiological study and pharmacokinetic study were adapted for evaluation of FODDS. Many studies have been carried out to illustrate the efficiency of the FODDS in overcoming the drawbacks such as poor bioavailability, drug wastage etc. Active agents derived from the field of pharmacognosy have also been benefited by FODDS since they prevent the enzymatic degradation of the active agents and and improve their bioavailability. FODDS also provides a robust pharmacokinetic profile with both in-vitro and in-vivo drug release rate which results in excellent in-vitro/in-vivo correlation due to its controlled release mechanism. This review is primarily focused on providing an overall insight into FODDS while giving detailed information regarding its design, development, mechanism, characterisation and a precise overview of various studies carried out using FODDS.

Enhanced sustained release of furosemide in long circulating chitosan-conjugated PLGA nanoparticles.

Furosemide (FSM) is commonly used in the treatment of edema associated with congestive cardiac failure, cirrhosis of the liver, renal disease, including the nephrotic syndrome and hypertension. However, in ascites, it is clinically limited due to its frequent dosing and short biological half-life and its prolonged-release preparations are not available. Therefore, the main objective behind the present research work is to develop chitosan coated and conjugated poly (lactic-co-glycolic acid) (PLGA) nanocarriers, to sustain the delivery of FSM with improved systemic circulation. Emulsion-solvent evaporation technique was used for the preparation of nanoparticles. In-vivo pharmacokinetic study showed 2.6, 3.10, and 4.30 folds enhancement in relative availability of FSM for FSM-PLGA, FSM-chitosan-coated-PLGA and FSM-chitosan-conjugated- PLGA nanoparticles, respectively than FSM. The present research work concluded that FSM loaded chitosan conjugated PLGA nanoparticles could enhance the systemic circulation of FSM with improved pharmacokinetics parameters.

Invivo Pharmacokinetic studies to investigate the enhancement of bioavailability of Lovastatin

The main aim of this study is to intensify the bioavailability of drug which is having lower bioavailability (<5 %) like Lovastatin in the form of Solid lipid nanoparticle (SLN) carrier and Nanostructured lipid carrier (NLC) and also to choose the best carrier molecule among this two by performing the invivo pharmacokinetic studies. The NLC (N3) and SLN (S6) was formulated by homogenization technique by using various formulation variable like lipid concentration (Witepsol) and surfactant concentration (span 80) and process variables like homogenization time (5000 Revolutions Per Minute) and albino wistar rats were used for the evaluation of invivo pharmacokinetic studies. From the obtained outcome, it was winded up that the formulation of Nanostructured Lipid Carried and SLN was carried out by a optimized hot homogenization technique. The optimized preparation N3 and S6 evaluated for invivo pharmacokinetic studies and compare the enhancing efficiency of bioavailability between the SLN and NLC. From the invivo pharmacokinetic data, NLC confirms enhancement of bioavailability by 10.56% when compared to SLN and conventional dosage form that have bioavailability 7.5% and 5.6%. From the outcome data of the research and in-vivo pharmacokinetic data, it came to an conclusion that the Lovastatin encapsulated Nanostructured Lipid Carrier presented an increased bioavailability than SLN, by intensifying the Area Under Curve and Mean Residence Time in plasma drug concentration profile. Hence using Nanostructured lipid carrier in the formulation of drugs in Biopharmaceutical Classification System class II, like Lovastatin which have low bioavailability will assure a better drug delivery system.

Trastuzumab decorated TPGS-g-chitosan nanoparticles for targeted breast cancer therapy.

Breast cancer, up-regulated with human epidermal growth factor receptor type-2 (HER-2) has led to the concept of developing HER-2 targeted anticancer therapeutics. Docetaxel-loaded D-α-tocopherol polyethylene glycol 1000 succinate conjugated chitosan (TPGS-g-chitosan) nanoparticles were prepared with or without Trastuzumab decoration. The particle size and entrapment efficiency of conventional, non-targeted as well as targeted nanoparticles were in the range of 126-186 nm and 74-78% respectively. In-vitro studies on SK-BR-3 cells showed that docetaxel-loaded non-targeted and HER-2 receptor targeted TPGS-g-chitosan nanoparticles have enhanced the cellular uptake and cytotoxicity with a promising bioadhesion property, in comparison to conventional formulation i.e., Docel™. The IC50 values of non-targeted and targeted nanoparticles from cytotoxic assay were found to be 43 and 223 folds higher than Docel™. The in-vivo pharmacokinetic study showed 2.33, and 2.82-fold enhancement in relative bioavailability of docetaxel for non-targeted and HER-2 receptor targeted nanoparticles, respectively than Docel™. Further, after i.v administration, non-targeted and targeted nanoparticles achieved 3.48 and 5.94 times prolonged half-life in comparison to Docel™. The area under the curve (AUC), relative bioavailability (FR) and mean residence time (MRT) were found to be higher for non-targeted and targeted nanoparticles when compared to Docel™. The histopathology studies of non-targeted and targeted nanoparticles showed less toxicity on vital organs such as lungs, liver, and kidney when compared to Docel™.

Dry powder inhaler formulations of poorly water-soluble itraconazole: A balance between in-vitro dissolution and in-vivo distribution is necessary

Formulating poorly water-soluble drug, itraconazole (ITZ), as dry powder inhaler (DPI) may be more effective for the treatment of invasive pulmonary Aspergillosis than intravenous injection and oral administration. It is necessary to improve the dissolution of ITZ because the alveolar lining fluid is limited and thus the dissolution of ITZ in the lung may be slow and incomplete. However, too fast dissolution may result in over-absorption into the circulation and thus insufficient distribution in the lung. The purpose of this study is to understand the relationship between in-vitro dissolution and in-vivo distribution of ITZ from DPI formulations. Two DPI formulations (F1 and F2) with identical compositions and similar aerodynamic behaviors were fabricated by hot melt extrusion and thus jet-milling. ITZ was formulated with mannitol as fine solid crystal suspension system to effectively improve its dissolution. In-vitro dissolution tests and in-vivo pharmacokinetic studies indicated that F1 released faster than F2 under both sink and non-sink conditions, but exhibited a lower lung retention and higher plasma absorption than F2. These results suggested that although dissolution enhancement of poorly water-soluble drugs in pulmonary delivery may be necessary to overcome problems such as local irritation and quick elimination by macrophages, it may have an impact on the distribution of the drug between the lung and the plasma. A balance between airway dissolution and systemic absorption should be taken into consideration when developing DPI formulations of poorly water-soluble ITZ.

A simplified and sensitive validated RP-HPLC method for determination of temozolomide in rat plasma and its application to a pharmacokinetic study

The present study describes the first fully validated RP-HPLC method for the quantification of temozolomide, an anti-cancer drug, in rat plasma. The method is simple, rapid, specific, sensitive and also environment-friendly. Further, the method can be translated for analysis with an LC-MS system with minor modifications. The procedure involved a simple step of protein precipitation for extraction of temozolomide and the internal standard, ganciclovir from the plasma. Efficient chromatographic separation was performed on reversed phase C-18 Oyster BDS Premium (5 μm, 4.6×150 mm) column using dual wavelength UV detector at 329 nm for temozolomide and 310 nm for the internal standard using a mobile phase consisting of a mixture of 0.5% aqueous acetic acid and methanol (98:2, v/v) in an isocratic mode at a flow rate of 1 mL/min. The method was sensitive with an LLOQ of 50 ng mL−1 and demonstrated good linearity from 50 to 10000 ng mL−1 with a regression coefficient of 0.998. The extraction efficiency was found to be >90.0% and all other validation parameters such as accuracy, precision and stability were well within limits. The method was successfully employed for the in-vivo pharmacokinetic study of temozolomide in rat.

Chitosan-Carboxymethyl-5-Fluorouracil-Folate Conjugate Particles: Microwave Modulated Uptake by Skin and MelanomaCells.

5-Fluorouracil delivery profiles in the form of chitosan-folate submicron particles through skin and melanoma cells invitro were examined using microwaves as the penetration enhancer. The invivo pharmacokinetic profile of 5-fluorouracil was also determined. Chitosan-carboxymethyl-5-fluorouracil-folate conjugate was synthesized and processed into submicron particles by spray-drying technique. The size, zeta potential, morphology, drug content, and drug release, as well as skin permeation and retention, pharmacokinetics, invitro SKMEL-28 melanoma cell line cytotoxicity, and intracellular trafficking profiles of drug/particles, were examined as a function of skin/melanoma cell treatment by microwaves at 2,450 MHz for 5+ 5 minutes. The level of skin drug/particle retention invitro and invivo increased in skin treated by microwaves. This was facilitated by the drug conjugating to chitosan and microwaves fluidizing both the protein and lipid domains of epidermis and dermis. The uptake of chitosan-folate particles by melanoma cells was mediated via lipid raft route. It was promoted by microwaves, which fluidized the lipid and protein regimes of the cell membrane, and this increased drug cytotoxicity. Invivo pharmacokinetic study indicated skin treatment by microwave-enhanced drug retention but not permeation. The combination of microwaves and submicron particles synergized skin drug retention and intracellular drug delivery.

Novel instantly-dispersible nanocarrier powder system (IDNPs) for intranasal delivery of dapoxetine hydrochloride: in-vitro optimization, ex-vivo permeation studies, and in-vivo evaluation

Dapoxetine (D) suffers from poor oral bioavailability (42%) due to extensive metabolism in the liver. The aim of this study was to enhance the bioavailability of D via preparing instantly-dispersible nanocarrier powder system (IDNPs) for intranasal delivery of D. IDNPs were prepared using the thin film hydration technique, followed by freeze-drying to obtain easily reconstituted powder providing rapid and ready method of administration. The produced nanocarrier systems were evaluated for drug content, entrapment efficiency percentage, particle size, polydispersity index, zeta potential, and drug payload. The optimized nanocarrier system was morphologically evaluated via transmission electron microscopy and the optimized freeze-dried IDNPs were evaluated for ex-vivo permeation and in-vivo pharmacokinetic studies in rabbits following intranasal and oral administration. The relative bioavailability of D after intranasal administration of freeze-dried IDNPs was about 235.41% compared to its corresponding oral nanocarrier formulation. The enhanced D permeation and improved bioavailability suggest that IDNPs could be a promising model for intranasal delivery of drugs suffering from hepatic first pass effect.

Optimization of proniosomal itraconazole formulation using Box Behken design to enhance oral bioavailability

The aim of our investigation was to study the combined impact of 3 independent variables on the development of itraconazole (ITR) proniosomes by using Box-Behnken design (BBD). BBD was implemented with 3 variable factors at 3 levels. The values of the factors and responses were exposed to multiple regressions to derive a second-order polynomial equation used to predict the values of optimized dependent variables (responses). The surfactant concentration, drug concentration and molar ratio (Span 60: cholesterol) were chosen as the independent variables. Fifteen proniosome formulae were prepared using the slurry method and estimated for drug entrapment efficiency (DEE), vesicle size (VZ) and % drug released after 8 h. The insignificant terms of the equation that showed the probability value (P > 0.05), were excluded from the full-model equation to attain a reduced-model equation to ease expecting the different responses upon changing variables. The effect of the different variables was also shown by the construction of line and contour plots. Two optimized formulae; P1 (0.28, 0.91 and −0.91) for the maximized response of DEE and % drug released without restriction of VZ and P2 (0.5, −1, −1) with a minimum VZ were prepared and evaluated for ex-vivo permeation study. In-vivo pharmacokinetic study of the optimized selected formula P2was tested against the market product (sporonox®) in rabbits. ITR Proniosomal formula showed 1.95 fold, 1.3 fold and 1.4 fold increase in Cmax, AUC0-48, and AUC0-∞, when compared to ITR market product. Our investigation suggested the potential use of proniosome as a drug carrier to enhance the bioavailability of ITR.

Laminated chitosan-based composite sponges for transmucosal delivery of novel protamine-decorated tripterine phytosomes: Ex-vivo mucopenetration and in-vivo pharmacokinetic assessments

In the current study, laminated chitosan (CS):hydroxypropyl methylcellulose (HPMC) composite sponges were exploited as solid matrices for buccal delivery of tripterine phytosomes functionalized with novel mucopenetrating protamine layer (PRT-TRI-PHY). Tripterine (TRI) is a herbal drug widely investigated as a potential anticancer candidate against various types of cancers. However, clinical use of TRI is handicapped by its low oral bioavailability. To surmount TRI pharmaceutical obstacles, TRI phytosomes (TRI-PHY) were prepared using solvent evaporation technique then coated with a protamine layer via electrostatic assembly process. The developed PRT-TRI-PHY showed a nano-metric size of 250 nm and positive zeta potential (+21.6 mV). Sponges loaded with PRT-TRI-PHY demonstrated a sustained release profile with superior mucoadhesion characteristics compared with the counterparts loaded with uncoated TRI-PHY. The ex-vivo permeation study via chicken pouch mucosa revealed that sponges loaded with PRT-TRI-PHY demonstrated 2.3-folds higher flux value compared with sponges loaded with uncoated TRI-PHY. Additionally, in-vivo pharmacokinetic study in healthy rabbits revealed the significantly higher bioavailability of PRT-TRI-PHY compared with TRI-PHY with relative bioavailability of 244%. Conclusively, mucoadhesive CS-HPMC sponges loaded with a novel mucopenetrating nanocarrier, PRT-TRI-PHY, could significantly improve the absorption of tripterine via buccal mucosa which would be of prime importance for its clinical utility.

Pharmacokinetic Studies of Gastroretentive Mucoadhesive Matrices for Diltiazem Hydrochloride Using Some Natural Polysaccharides

The objective of this study was to investigate differences in the pharmacokinetic patterns between a gastroretentive mucoadhesive drug delivery system (GRMDDS) and sustained release dosage form of same dose to increase the residence time of the drug in to the stomach and release for extended period of time. Gastroretentive mucoadhesive tablets of diltiazem hydrochloride (DLTH) with hibiscus esculentus mucilage and xanthan gum as natural polysaccharides were developed for mucoadhesive sustained drug release by wet granulation technique. In-vivo gastro retentive mucoadhesion study confirmed stomach retention for more than 10 h. In-vivo pharmacokinetic studies in rabbits showed Cmax of 176.86 ng/ml and Tmax of 13.3 h for GRMDDS. AUC0–t and AUC0–8 for mucoadhesive tablet formulation was 2514.61 and 3145.77 while the marketed formulation was 2220.11 and 2750.36 ng.h/ml respectively. The point estimates (90% CI) of the “test/reference” mean ratio for Cmax, AUC0-t and Tmax were 1.0662, 1.0327 and 1.33. The difference for AUC0–t and AUC0–8 between the test and reference formulation was statistically significant (p<0.05). Non superimposition of the percent in-vivo absorption and in-vitro dissolution curves was observed to investigate a multiple point correlation of in-vivo and in-vitro which might suggest the possibility of the existence of a level A correlation using the optimum dissolution condition. The results of the present study indicate that the oral bioavailability of diltiazem hydrochloride is significant increase when its dosage is provided prolonged gastric residence by GRMDDS.

Oral bioavailability enhancement of raloxifene by developing microemulsion using D-optimal mixture design: optimization and in-vivo pharmacokinetic study

The objective of this work was to utilize a potential of microemulsion for the improvement in oral bioavailability of raloxifene hydrochloride, a BCS class-II drug with 2% bioavailability. Drug-loaded microemulsion was prepared by water titration method using Capmul MCM C8, Tween 20, and Polyethylene glycol 400 as oil, surfactant, and co-surfactant respectively. The pseudo-ternary phase diagram was constructed between oil and surfactants mixture to obtain appropriate components and their concentration ranges that result in large existence area of microemulsion. D-optimal mixture design was utilized as a statistical tool for optimization of microemulsion considering oil, Smix, and water as independent variables with percentage transmittance and globule size as dependent variables. The optimized formulation showed 100 ± 0.1% transmittance and 17.85 ± 2.78 nm globule size which was identically equal with the predicted values of dependent variables given by the design expert software. The optimized microemulsion showed pronounced enhancement in release rate compared to plain drug suspension following diffusion controlled release mechanism by the Higuchi model. The formulation showed zeta potential of value −5.88 ± 1.14 mV that imparts good stability to drug loaded microemulsion dispersion. Surface morphology study with transmission electron microscope showed discrete spherical nano sized globules with smooth surface. In-vivo pharmacokinetic study of optimized microemulsion formulation in Wistar rats showed 4.29-fold enhancements in bioavailability. Stability study showed adequate results for various parameters checked up to six months. These results reveal the potential of microemulsion for significant improvement in oral bioavailability of poorly soluble raloxifene hydrochloride.

Brain Targeting of 1,9-Pyrazoloanthrone an c-Jun-N-terminal Kinase Inhibitor Using Liposomes for Effective Management of Parkinson's Disease.

The major challenge to treat Parkinson's disease (PD) is penetration of target molecule into the brain to improve the efficacy of drugs. To achieve better brain penetration and targeted delivery, 1,9-Pyrazoloanthrone (1,9-P) loaded liposomes were developed by solvent injection technique using ultrasonication and evaluated for particle size, morphology, entrapment efficiency, FT-IR, and in-vitro drug release studies. The potential of 1,9-Pyrazoloanthrone (1,9-P), a c-Jun-N-terminal Kinase (JNK-3) inhibitor which could stop or retard the rate of apoptosis of neuronal cells was also evaluated. In-vivo pharmacokinetic and brain uptake studies of liposomes were performed to investigate the bioavailability and brain distribution of 1,9-P. Cytotoxicity and neuroprotection were done on SH-SY5Y cell line using MTT and AO/EB apoptosis assay. The optimized batch of liposomes showed an average size of 112.33 ± 0.84 nm with a zeta potential value of -19.40 mV and 78.96 ± 0.28% drug entrapment efficiency. The in-vitro release studies demonstrated the sustained release profile of liposome up to 24 h. The pharmacokinetic data in Wistar rats over the period of 12 h demonstrated 4.82-folds greater AUC(0-12 h) for liposome in brain compared with 1,9-P suspension. Cytotoxicity assay showed no sign of toxicity, whereas apoptosis assay revealed a neuroprotective action of liposomes. The results demonstrated successful targeting of the 1,9-P, to brain as a novel strategy having significant therapeutic potential to treat PD.

Design, Development and Invivo Pharmacokinetic Evaluation of Cardiovascular Drug Loaded Nano Structured Lipid Carrier System

The Present investigation is to design, develop and optimize the Nanostructured Lipid Carrier (NLC) containing cardiovascular drug by various independent variables like formulation variables (concentration of phospholipids, surfactants, co-surfactant) and process variables (homogenization time and ultrasonication time). The objective of this research is to choose the suitable and reproducible technique for the formulation of NLC based on dependent variables like Particle Size (PS) in nm, Polydispersity Index (PDI), Zeta potential (ZP) in mV and Entrapment efficiency (EE%) by applying Box Behnken design utilizing - Multiple linear regression method (Design expert 9 software, stat-ease, Inc. USA) and another objective is to prove the enhancement of bioavailability of drug in developed NLC. Comparative invivo pharmacokinetic studies was carried out to determine AUC, Cmax, Tmax , Ke, Vd between drug loaded NLC and commercially available dosage form to prove the enhancement of bioavailability in NLC. From the results obtained, it was concluded that hot homogenization was an optimized technique for the preparation of NLC containing carvedilol and NLC shows better bioavailability when compare to commercial formulation. This data was related to the research project sanctioned by Department of science and technology (DST) entitled “Development of Lipid Nanoparticles Enriched Hydrogels for Transdermal Drug Delivery: Formulation, In vitro Characterization and Pharmacodynamic studies in Animals”

Fabrication and in-vivo evaluation of lipid nanocarriers based transdermal patch of colchicine

The present study deals with the formulation and evaluation of Solid Lipid Nanoparticles (SLNs) based transdermal patch of colchicine. Colchicine loaded SLNs (C-SLNs) were prepared by ultrasonication method and optimized with respect to the concentration of lipid and surfactant by 32 full factorial design. Properties like particle size, shape, zeta potential, polydispersity index and percentage entrapment efficiency were determined. The transdermal potential of C-SLNs was evaluated by ex-vivo drug permeation using Wistar rat skin and fluorescence microscopy. The optimized formulation was fabricated into the transdermal patch and in-vivo pharmacokinetic and pharmacodynamic study (subcutaneous air pouch model) was carried out. Particle size, zeta potential and entrapment efficiency of the optimized formulation were found to be 107 nm, (−) 17.4 mV and 37.25% respectively. Formulation F5 showed highest transdermal flux (8.76 μg/cm2/hrs). Fluorescence study confirms that SLNs have more penetration potential through the skin. AUC0→∞ of C-SLNs patch was improved by 2.84 times more than colchicine patch. Significant (p < 0.001) reduction in exudate volume, leukocyte count, and collagen deposition was observed in animals treated with C-SLNs transdermal patch. Thus, SLNs based transdermal patch of colchicine could be a promising approach for the treatment of gout.

Efavirenz loaded nanostructured lipid carrier engineered for brain targeting through intranasal route: In-vivo pharmacokinetic and toxicity study

Intranasal delivery is a potential platform that can be employed in targeting the antiretrovirals (ARVs) to reach HIV that harbors in the central nervous system. The objective of the study was to develop an optimized efavirenz (EFV) loaded nanostructured lipid carrier (ENLC) and deliver it through intranasal route for brain targeting. Factorial design (23) was used to identify the key formulation variables influencing particle size and percent drug encapsulation of efavirenz in the NLC. Optimised ENLC-6 batch exhibited a spherical morphology with a mean particle size of 162nm, high drug encapsulation of 95.78±0.42% and in-vitro drug release of 92.45% at the end of 24h. Single dose in-vivo pharmacokinetic studies revealed significant therapeutic concentration of the drug in the CNS following IN administration with a Cmax value of 31.45±0.75 and T1/2 of 11.14h. A 10 fold increase (p<0.001) in% drug targeting efficiency (DTE) and 4.5 fold increase (p<0.001) in % drug targeting potential (DTP) for ENLC-6 was observed as compared to pure EFV. Sub-acute 28day IN toxicity in experimental animals indicated non-toxicity of encapsulated efavirenz over pure drug. Based on the findings we conclude that the intelligent choice of the lipdic carrier along with the strategic use of excipients can prove helpful for the efficient brain targeting of the encapsulated efavirenz which is devoid of toxicity. This may prove useful in the management of neuro-AIDS.

Formulation and characterization of chitosan encapsulated phytoconstituents of curcumin and rutin nanoparticles

Curcumin and Rutin are natural polyphenolic molecules exhibits several pharmacological actives like antibacterial, anticancer, antioxidant, chemo-preventive and anti-inflammatory properties. However till date, no studies have been reported on their combination efficacy, especially in treating multi-drug resistance of cancers because of their poor solubility and bioavailability. Hence in the present study, an attempt has been made to load both these drugs into a single nanoparticlulate system to enhance their bioavailability and efficacy. This novel formulation was prepared by solvent evaporation technique and was evaluated for particle size and shape using Zeta Sizer, Scanning Electron Microscopy (SEM) and Fourier Transform Infra Red (FT-IR) Spectroscopy. The optimized formulation was further subjected to in vitro and in vivo evaluations. The prepared nanoparticles were in the size range of 25–100nm and the release profile was found to be Non −Fickian transport. In-vivo pharmacokinetic studies were carried in rabbits and the pharmacokinetic profile was studied. The results indicate that oral bioavailability of Curcumin and Rutin has been increased to 3.06 and 4.24 folds respectively when compared to their pure drugs. This data suggest that the present novel nanoparticles loaded with these combinational drugs may have better therapeutic potential in treating drug resistant cancers.