In-vivo Pharmacokinetic Study Research Articles

Solid Self Nano-Emulsifying Drug Delivery System of Dasatinib: Optimization, In-vitro, Ex-vivo and In-vivo assessment.

Aim: Dasatinib (DST) is an oral tyrosine kinase inhibitor with poor aqueous solubility. To outwit this issue, a solid self-nano emulsifying drug delivery system (S-SNEDDS) of DST was formulated.Methods: I-optimal mixture design was used for optimization of DST-loaded SNEDDS using Linalool, Cremophor RH40 and Transcutol P. S-SNEDDS underwent physicochemical characterization, in-vitro release and ex-vivo permeation, cell-based assays and pharmacokinetic study.Results: DST-S-SNEDDS showed globule size and PDI of 141.53±5.371nm and 0.282±0.020, respectively. DST-S-SNEDDS revealed significantly lower IC50 (1.825μg/mL) than free DST (7.298μg/mL) in MDA-MB-231. In-vivo pharmacokinetic study revealed 1.94-fold increment in AUC0-t for the DST-S-SNEDDS group than free DST.Conclusion: S-SNEDDS could be promising approach for improving bioavailability and efficacy of DST.

Exploring nalbuphine loaded chitosan nanoparticles for effective pain management through intranasal administration: a comparative study

Background Intranasal drug delivery shows potential for brain access via olfactory and trigeminal routes. Purpose This work aimed to ensure brain availability of nalbuphine via the nasal route. Method Chitosan based nanoparticles loaded with nalbuphine were successfully prepared using ionic gelation method and characterised. Result SEM results revealed that the nanoparticles were spherical in shape, with an average size of 192.4 ± 11.6 nm. Zeta potential and entrapment efficiency was found 32.8 mV and 88.43 ± 7.75%, respectively. The X-ray diffractometry and DSC results unravel a profound understanding on the physical and thermal characteristics. The in-vitro release of nalbuphine from the nanoparticles was biphasic, with an initial burst release followed by a slow-release profile. In-vitro cell study on HEK-293 cells and microscopic images of brain tissue confirmed the safety profile of formulation. In-vivo efficacy studies on animal confirmed the effectiveness of developed intranasal formulation as compared to the standard therapy. The in-vivo pharmacokinetic studies showed that the prepared nanoparticles were able to efficiently deliver nalbuphine to the brain in comparison to the other body organs. Gamma scintigraphy images showed retention of the drug in the brain. Furthermore, the efficacy studies confirmed that the nanoparticles were found significantly more effective than the marketed formulation in pain management.

Nose-to-brain delivery of nano-engineered biomaterials for effective targeting to the brain

Thermoresponsive hydrogels provide a platform for sustained delivery of nanoparticles via nose-to-brain route by resisting mucociliary clearance to the enhanced mean residence time (MRT) of the formulation in the nasal cavity overcoming neurotoxicity induced by uncontrolled delivery of nanoparticles and accumulation in the brain when delivered alone. The reported study presents the synthesis of pullulan (PLN) based nanoparticles (PNP-EHBr) loaded with eletriptan hydrobromide (EHBr) via ionic gelation method having size between 26.65 nm and 29.59 nm after stability studies of 4 h incubation with an average zeta potential of 22.5 ± 0.1 mV and entrapment efficiency of 92.048%. F-127/F-68 based hyaluronic acid-co-pectin hydrogels of EHBr-loaded PLN nanoparticles thermoresponsive hydrogels (HAP-PNP-EHBr/T-Hg) were characterized via Fourier transform infrared spectroscopy (FTIR), X-ray diffraction, thermal analysis (TGA/DSC), and scanning electron microscopy and evaluated for their gelation time, gelation temperature, gel strength, cloud point, sol–gel fraction, ex-vivo permeation, etc. HAP-PNP-EHBr/T-Hg showed drug release in a controlled pattern in both phosphate-buffered saline (PBS) and simulated nasal fluid (SNF) i.e., 90.12 and 87.99, respectively, over 48 h, while PNP-EHBR, 99.44 and 97.53 in PBS and SNF, respectively, over 8 h. The controlled release and absorption of EHBr from HAP-PNP-EHBr/T-Hg and PNP-EHBr was estimated by an in-vivo pharmacokinetic study using high-performance liquid chromatography, MRT and area under the curve (AUC) were increased up to 11.337 ± 0.32 h and 3,104.73 ± 75.841 ng/mL*h, 11.088 ± 0.177 h and 3,906.64 ± 152.86 ng/mL*h in brain and blood respectively after IN administration. This work demonstrates the successful synthesis of a twofold drug delivery system with PLN-based nanoparticles (PNP-EHBr) loaded with EHBr laden F-127/F-68 based hyaluronic acid-co-pectin hydrogels (HAP-PNP-EHBr/T-Hg).

Development, optimization, and in-vivo bioavailability study of erlotinib hydrochloride loaded microsponge for colon targeting

The present investigation aimed to develop as well as optimize microsponge containing erlotinib hydrochloride (ETB) that was composed of ethyl cellulose (EC) and pectin. The water solubility and enzymatic susceptibility make it easier to fabricate the microsponge formulation. The ETB loaded microsponge was manufactured using quasi-emulsion solvent diffusion process. By this technique, organic solution of the primary component is emulsified with stabilizing agents that are soluble in water. To design the formation of the microsponge, 32 factorial design was implemented. It was investigated how the response variables like particle dimension, entrapment efficiency, ETB diffusion at 12 ​h were influenced by independent variables such as rotation speed and the pectin to ethyl cellulose ratio. The optimal microsponge formulation loaded with ETB (F0) composed of 1:2.8 ratio of pectin to ethyl cellulose (EC) with stirring rate at 478 ​rpm. Particle dimension, entrapment efficiency, and ETB release at 12 ​h from optimized formulation were shown 104.89 ​± ​0.62 ​nm, 82.36 ​± ​2.85 ​%, and 85.49 ​± ​1.84 ​% respectively. The In-vivo pharmacokinetic study conducted on rabbit model shows a significant improvement in bioavailability. The optimized microsponge formulation has been found to have a higher Cmax than the ETB aqueous suspension. The stability of the formulation has been determined by the accelerated stability study of optimized microsponge formulation. This study indicated that the optimized formulation retained its stability even after 90days. In general, the present investigation demonstrated that drug loaded microsponge based formulation is a suitable method to improve the therapeutic efficacy and bioavailability of ETB.

In-vivo pharmacokinetic study of ibrutinib-loaded nanostructured lipid carriers in rat plasma by sensitive spectrofluorimetric method using harmonized approach of quality by design and white analytical chemistry

Ibrutinib, an antineoplastic agent tackling chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom’s Macroglobulinemia, falls under the category of BCS class II drugs, characterized by a puzzling combination of low solubility and high permeability. Its oral bioavailability remains a perplexing challenge, merely reaching 2.9 % due to formidable first-pass metabolism hurdles. In a bid to surmount this obstacle, researchers embarked on a journey to develop ibrutinib-loaded NLCs (Nanostructured Lipid Carriers) using a methodology steeped in complexity: a Design of Experiments (DoE)-based hot melted ultrasonication approach. Despite a plethora of methods for analyzing ibrutinib in various matrices, the absence of a spectrofluorimetric method for assessing it in rat plasma added to the enigma. Thus emerged a spectrofluorimetric method, embodying principles of white analytical chemistry and analytical quality by design, employing a Placket-Burman design for initial method exploration and a central composite design for subsequent refinement. This method underwent rigorous validation in accordance with ICH guidelines, paving the way for its application in scrutinizing the in-vivo pharmacokinetics of ibrutinib-loaded NLCs, juxtaposed against commercially available formulations. Surprisingly, the optimized NLCs exhibited a striking 1.82-fold boost in oral bioavailability, shedding light on their potential efficacy. The environmental impact of this method was scrutinized using analytical greenness tools, affirming its eco-friendly attributes. In essence, the culmination of these efforts has not only propelled advancements in drug bioavailability but also heralded the dawn of a streamlined and environmentally conscious analytical paradigm.

P-gp inhibition and enhanced oral bioavailability of amikacin Sulfate: A novel approach using Thiolated Chito-PEGylated Lipidic Hybrids

This study aimed to develop oral lipidic hybrids of amikacin sulfate (AMK), incorporating thiolated chitosan as a P-glycoprotein (P-gp) inhibitor to enhance intestinal absorptivity and bioavailability. Three formulations were designed: PEGylated Liposomes, Chitosan-functionalized PEGylated (Chito-PEGylated) Lipidic Hybrids, and Thiolated Chito-PEGylated Lipidic Hybrids. The physical characteristics of nanovesicles were assessed. Ex-vivo permeation and confocal laser scanning microscopy (CLSM) studies were conducted to evaluate the formulations’ potential to enhance AMK intestinal permeability. In-vivo pharmacokinetic studies in rats and histological/biochemical investigations assessed the safety profile and oral bioavailability. The AMK-loaded Thiolated Chito-PEGylated Lipidic Hybrids exhibited favorable physical characteristics, higher ex-vivo permeation parameters, and verified P-gp inhibition via CLSM. They demonstrated heightened oral bioavailability (68.62% absolute bioavailability) and a sufficient safety profile. Relative bioavailability was significantly higher (1556.3% and 448.79%) compared to PEGylated Liposomes and Chito-PEGylated Lipidic Hybrids, respectively, indicating remarkable oral AMK delivery with fewer doses, reduced side effects, and enhanced patient compliance.

Fabrication, optimization, and evaluation of lyophilized lacidipine-loaded fatty-based nanovesicles as orally fast disintegrating sponge delivery system

Lacidipine (LCD) is a potent antihypertensive agent. Fatty-based nanovesicles (FNVs) were designed to improve LCD low solubility and bioavailability. LCD-FNVs were formulated according to different proportions of cetyl alcohol, cremophor®RH40, and oleic acid adopting Box-Behnken Design. The optimized LCD-FNVs, composed of cetyl alcohol 48.4 mg, cremophor®RH40 120 mg, and oleic acid 40 mg, showed minimum vesicle size (124.8 nm), maximum entrapment efficiency % (91.04 %) and zeta potential (-36.3 mV). The optimized FNVs were then used to formulate the lyophilized orally fast-disintegrating sponge (LY-OFDS). The LY-OFDS had a very short disintegration time (58 sec), remarkably high % drug release (100 % after 15 mins), and increased the drug transbuccal permeation by over 9.5-fold compared to the drug suspension. In-vivo evaluation of antihypertensive activity in rats showed that the LY-OFDS reduced blood pressure immediately after 5 min and reached normal blood pressure 4.5-fold faster than the marketed oral tablets. In the In-vivo pharmacokinetic study in rabbits, the LY-OFDS showed 4.7-fold higher bioavailability compared with the marketed oral tablet. In conclusion, the LY-OFDS loaded with LCD-FNVs is a safe, and non-invasive approach that can deliver LCD effectively to the blood circulation via the buccal mucosa giving superior immediate capabilities of lowering high blood pressure and increasing the drug bioavailability.

Synthesis of salcaprozate sodium and its significance in enhancing pancreatic kininogenase absorption performance.

We conducted pharmacokinetic research wherein salcaprozate sodium (SNAC) was utilized as a penetration enhancer by incorporating it into pancreatic kininogenase (PK) to improve the bioavailability of pancreatic kininogenase enteric-coated tablets. We conducted invitro studies on PK using the Caco-2 cell model and quantified PK levels using the enzyme-linked immunosorbent assay (ELISA) method. We conducted methodological verification by blending SNAC and PK powders into enteric-coated capsules, and studied the pharmacokinetic characteristics. Based on the PK transport assay, the cumulative permeation rates of the test group that employed a SNAC to PK ratio of 32:1, 16:1, 8:1, 4:1, and 2:1 were 13.574%, 7.597%, 10.653%, 3.755%, and 2.523%, respectively. We conducted a uniformity test on the powder that contained a blend of SNAC and PK. The relative standard deviations (RSDs) for both the power containing SNAC and the power not containing SNAC were less than 10%. Based on the methodological verification, invivo pharmacokinetic study of PK met the experimental requirements. As indicated by the results of invivo pharmacokinetic research on rats, the test group (This group used SNAC) had a PK AUC0-12 h of 5679.747 ng/L*h and t1/2 of 4.569 h, while the control group (This group did not use SNAC) had a PK AUC0-12 h of 4639.665 ng/L*h and t1/2 of 3.13 h. This study has established a low-cost, environmentally friendly, and safe SNAC synthesis route with high process yield suitable for industrial production. SNAC demonstrates an absorption-enhancing effect on PK, and the optimal ratio of SNAC to PK is determined to be 32:1.

Appraisal of folate functionalized bosutinib cubosomes against hepatic cancer cells: In-vitro, In-silico, and in-vivo pharmacokinetic study

Targeted therapies enhance the efficacy of tumour screening and management while lowering side effects. Multiple tumours, including liver cancer, exhibit elevated levels of folate receptor expression. This research attempted to develop surface-functionalised bosutinib cubosomes against hepatocellular carcinoma. The novelty of this work is the anti-hepatic action of bosutinib (BST) and folic acid-modified bosutinib cubosomes (BSTMF) established through proto-oncogene tyrosine-protein kinase (SrC)/ focal adhesion kinase(FAK), reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and cell cytotoxicity. Later, the in-vivo pharmacokinetics of BSTMF were determined for the first time. The strong affinity of folic acid (FA) for folate receptors allows BSTMF to enter cells via FA receptor-mediated endocytosis. The particle size of the prepared BSTMF was 188.5 ± 2.25 nm, and its zeta potential was −20.19 ± 2.01 mV, an encapsulation efficiency of 90.31 ± 3.15 %, and a drug release rate of 76.70 ± 2.10 % for 48 h. The surface architecture of BSTMF was identified using transmission electron microscopy (TEM) and Atomic force microscopy (AFM). Cell-line studies demonstrated that BSTMF substantially lowered the viability of Hep G2 cells compared to BST and bosutinib-loaded cubosomes (BSTF). BSTMF demonstrated an elevated BST concentration in tumour tissue than in other organs and also displayed superior pharmacokinetics, implying that they hold potential against hepatic cancers. This is the first study to show that BSTMF may be effective against liver cancer by targeting folate receptors and triggering SrC/FAK-dependent apoptotic pathways. Multiple parameters demonstrated that BSTMF enhanced anticancer targeting, therapeutic efficacy, and safety in NDEA-induced hepatocellular carcinoma.

Development of venetoclax with 2-hydroxypropyl-beta-cyclodextrin inclusion complex for improved bioavailability

Cyclodextrin complexes loaded with venetoclax for improved solubility and therapeutic efficacy as repurposed drug. The venetoclax-cyclodextrin inclusion complex was prepared using kneading method. Primarily in-silico molecular docking study was performed to examine the possible interaction between venetoclax and hydroxypropyl-β-cyclodextrin (HP-β-CD) and extensively characterized. The in-vitro studies were performed using A-549 lung epithelial cancer cells. The in-vivo pharmaco-kinetic studies was performed on wistar rats. The aqueous solubility of venetoclax was increased upto 3.16 folds, as compared with pure venetoclax with entrapment efficiency (EE%) was determined 95.44 ± 0.3%. In-vitro cytotoxicity studies were carried on A-549 lung epithelial cancer cells, wherein BCL-2 receptors were highly over-expressed and IC 50 values for venetoclax and venetoclax- HP-β-CD complex was calculated at 24 and 48 hrs in the order of 1.241 µg/ml, 0.68 µg/ml and 0.757719 µg/ml, 0.6125 µg/mL, respectively. The oral bioavailability was increased 4.03 times compared to the pure drug. The venetoclax-HP-β-CD inclusion complexes showed the increased aqueous solubility with improved anticancer activities. Communicated by Ramaswamy H. Sarma

Microneedle-assisted transdermal delivery of carvedilol nanosuspension for the treatment of hypertension

Carvedilol nanosuspension loaded microneedles patch was formulated and characterized by particle size, zeta potential, solubility, Transmission Electron Microscopy, X-Ray Diffraction, in-vitro release and in-vivo pharmacokinetic studies

Pharmacokinetic assessment of Natural Anticancer Berberine Chloride in presence and absence of some Herbal Bioenhancers in rabbit model

The present study investigated the influence of pretreatment of herbal bioenhancers quercetin, curcumin and piperine, separately on pharmacokinetic profile of berberine chloride (BBC) in rabbit model. Initially, ex-vivo permeability studies were conducted to optimize the batches of drug and bioenhancer combinations, wherein, the optimized batches were subjected for in-vivo pharmacokinetic studies in rabbits via single oral dose. All experimental procedures on animals were conducted according to the CPCSEA guidelines. The collection of blood samples were done at predetermined time intervals appropriately processed and analyzed by HPLC method. The data were processed using software and pharmacokinetic parameters (AUC, Cmax, Tmax, Kel) of BBC were obtained. The results showed that piperine exhibited strongest bioenhancing effect on BBC absorption as compared to quercetin and curcumin. The Cmax of BBC was increased by 626.53%, 401.86% and 168.60% for piperine, quercetin and curcumin optimized batches, respectively, with notable reduction in Tmax as compared to BBC (Control). These bioenhancers showed outstanding enhancement in the pharmacokinetic profile of BBC. BBC has been reported to be P-glycoprotein (P-gp) substrate, exhibiting extremely poor bioavailability, which could be successfully overcome by pre-treatment with bioenhancers, attributed to bioenhancer mediated inhibition of the P-gp efflux pump and drug metabolizing enzymes. This improvement in bioavailability and other pharmacokinetic parameters of BBC in presence of bioenhancers would be expected to reduce dose, dosing frequency and toxicity of BBC, thereby contributing improved patient compliance. Thus, it could be concluded that, pre-treatment of herbal bioenhancers could be an effective approach to improve pharmacokinetics of drug like molecules.

Design, Synthesis, and Antisickling Investigation of a Thiazolidine Prodrug of TD-7 That Prolongs the Duration of Action of Antisickling Aromatic Aldehyde.

The synthetic allosteric effector of hemoglobin, TD-7 has been investigated as a potential therapeutic agent for the treatment of sickle cell disease. The pharmacologic activity of TD-7 is due to formation of a Schiff-base interaction between its aldehyde group and the two N-terminal αVal1 amines of hemoglobin, effectively inhibiting sickling of red blood cells. However, TD-7 faces a challenge in terms of poor oral bioavailability due to rapid in-vivo oxidative metabolism of its aldehyde functional group. To address this shortcoming, researches have explored the use of a L-cysteine ethyl ester group to cap the aldehyde group to form a thiazolidine aromatic aldehyde prodrug complex, resulting in the improvement of the metabolic stability of this class of compounds. This report details the synthesis of a thiazolidine prodrug of TD-7, referred to as Pro-7, along with a comprehensive investigation of Pro-7 functional and biological properties. In an in-vitro Hb modification and Hb oxygen affinity studies using normal whole blood, as well as erythrocyte sickling inhibition using sickle whole blood, Pro-7 exhibited a gradual onset but progressive increase in all activities. Additionally, in-vivo pharmacokinetic studies conducted with Sprague Dawley rats demonstrated that Pro-7 can undergo hydrolysis to release TD-7. However, the blood concentration of TD-7 did not reach the desired therapeutic level. These findings suggest that the incorporation of the L-cysteine ethyl ester group to TD-7 represents a promising strategy to enhance the metabolic stability of aromatic aldehydes that could lead to the development of a more effective drug for the treatment of sickle cell disease.

Comparison of In Vitro Corneal Permeation and In Vivo Ocular Bioavailability in Rabbits of Three Marketed Latanoprost Formulations.

All latanoprost formulations currently available for the treatment of glaucoma or ocular hypertension contain the same concentration of latanoprost (0.005%) but differ in excipients, which may affect corneal drug permeability or stability. This study aimed at comparing corneal penetration of three marketed latanoprost solutions with different excipient formulations in invitro and invivo drug permeability studies. Three latanoprost formulations were tested under good laboratory practice conditions: a formulation containing benzalkonium chloride (BAK) but no surfactant (Preserved latanoprost); the same formulation except preservative-free (PF) without BAK or surfactant (SF) (PF SF latanoprost); and a different formulation without BAK but containing a non-ionic surfactant (MGHS 40 at 5%) combined with thickening agents (Carbomer 974P, Macrogol 4000) (PF latanoprost). Corneal permeation of latanoprost acid (LAT) was first determined invitro using a reconstructed human corneal epithelium tissue. Then, invivo pharmacokinetic studies were performed on pigmented rabbits, for which LAT concentration was measured in the aqueous humour (AH) and iris-ciliary body (ICB). Invitro, the cumulative transport of LAT was linear between 1h and 4h for preserved latanoprost and PF SF latanoprost, and LAT concentrations matched exactly at each timepoint. By contrast, the permeation of PF latanoprost was linear between 2h and 12h and was significantly lower than that of preserved latanoprost and PF SF latanoprost at 4 and 8h (p<0.001). In rabbits, the concentrations of LAT in AH and ICB were not statistically different between preserved latanoprost and PF SF latanoprost at each timepoint, except at 1h in ICB (p=0.005). By comparison, the LAT concentration of PF latanoprost was statistically (p<0.05) lower than that of preserved latanoprost and PF SF latanoprost in AH and ICB from 0.5 to 3h. BAK did not influence the corneal penetration of latanoprost in invitro and invivo studies. The formulation containing a non-ionic surfactant resulted in lower and slower ocular penetration compared with preserved or PF SF formulations. This raises questions about the relevance of BAK and some surfactants in enhancing corneal penetration of ocular formulations.

Evaluation of methotrexate encapsulated polymeric nanocarrier for breast cancer treatment

Herein, Methotrexate-loaded chitosan nanoparticles (Meth-Cs-NPs) was formulated through single-step self-assembly by incorporating the ionic-gelation method. Chitosan was cross-linked with Methotrexate via a sodium tripolyphosphate (STPP) where 49 % Methotrexate was loaded in the nanoparticles (∼143 nm) and zeta potential of 34 ± 3 mV with an entrapment efficiency of 87 %. The efficacy of nanoparticles was assessed for chemically induced breast cancer treatment in the Sprague Dawley rats model. These Meth-Cs-NPs followed the Korsmeyer-Peppas model in-vitro release kinetics. Nanoparticles were further evaluated for in-vitro efficacy on triple-negative breast cancer (MDA-MB-231) cell lines. The MTT assay studies revealed that even slight exposure to Meth-Cs-NPs (IC50 = 15 µg/mL) caused 50 % cell death in 24 h. Further, hemocompatibility studies of Meth-Cs-NPs were performed, deciphered that Meth-Cs-NPs were biocompatible (hemolysis < 2 %). Additional cellular uptake was evaluated by confocal imaging. Moreover, an in-vivo pharmacokinetic study of nanoparticles in rats displayed increased plasma concentration of the drug and retention time, whereas a decrease in cellular clearance compared to free Methotrexate. Further, anti-tumor efficacy studies revealed that nanoparticles could reduce tumor volume from 1414 mm3→385 mm3 compared to free Methotrexate (1414 mm3→855 mm3). The current study presents encouraging prospects of Meth-Cs-NPs to be used as a viable breast cancer treatment modality.

Microfabrication and Characterization of Chemically Actuated Implantable PLGA Reservoir-based Device for Controlled Drug Delivery

This paper proposes the fabrication and characterization of the drug delivery device (DDD) that is capable of delivering the drug to the target site using bio-degradable polymer. The insulin used as a model drug in this study was loaded into the microreservoir (5 mm * 5 mm * 0.5 mm) which was fabricated using Poly-Lactic-Co-Glycolic acid (PLGA) polymer. The permeation of the drug solution and the release rates were controlled by varying the thickness of the biodegradable membrane. The fabricated DDD was designed to deliver about 20 µL of the drug. Implantable formulations of insulin were generated using biodegradable polymer PLGA, which were further tested by loading different quantities of the drug. The activity of the implant was tested using in-vitro release by taking Phosphate-buffered saline (PBS), as well as in-vivo pharmacokinetic studies in Wistar rats. Insulin-loaded implants were inserted under the skin layer by minor surgery. The blood samples were collected at different time intervals, which were further analyzed by High-performance liquid chromatography (HPLC). The obtained results confirmed the presence of insulin in the blood by showing a retention time (RT) of 2.8 min at λ max of 280 nm. The results have shown that the insulin was found in the blood after 4 h of implant insertion and remained up to 48 h. This study clearly suggests that the fabricated device can be used for the successful delivery of insulin in the blood. The use of this DDD bypasses the degradation of insulin in the stomach and thus can be used as an effective drug carrier system for the delivery of insulin.

Spherical crystal agglomeration technique for improved flow properties and oral bioavailability of atazanavir sulphate.

Aim: The current research focused on formulation of spherical crystal agglomerates (SCA) of atazanavir sulphatefor improving flow property and solubility. Materials & methods: SCA were formulated by quasi-emulsification solvent diffusion. Methanol, water and dichloromethane were employed as a good solvent, bad solvent and bridging liquid respectively. Results & conclusion: SCA with improved solubility and micromeritic properties were directly compressed into a tablet. The SCA tablets had higher dissolution rates compared with plain drug and marketed product. Invivo pharmacokinetic studies revealed higher Cmax and AUC0-t of the SCA than marketed product with relative bioavailability of 1.74. The formulation was stable for more than 3months, with insignificant difference in % drug content and % drug dissolution.

Enhanced Pharmacokinetics and Anti-inflammatory Activity of Curcumin Using Dry Emulsion as Drug Delivery Vehicle.

Many naturally available dietary molecules such as curcumin have not seen the market due to poor solubility, bioavailability, and photodegradability. Successful development of a lipid-based dry emulsion may overcome these issues and help in reaching the markets for natural dietary molecules such as curcumin. The current study aims to develop a dry emulsion formulation of curcumin using natural oil and evaluate its dissolution, photostability, pharmacokinetics, and anti-inflammatory activity. Dry emulsions were prepared using emu oil and corn oil as the lipid phase, Caproyl 90 and Cremophor RH 40 as surfactants, and dextrin as a hydrophilic carrier. Microscopic studies showed the formation of spherical porous particles, and solid-state characterization using differential scanning calorimetry and powder X-ray diffraction showed the conversion of curcumin to an amorphous form. About 80% drug release was observed from formulation, whereas pure drug showed only 50% drug release in 30min. Invivo pharmacokinetic studies showed fivefold improvement in the maximum concentration of curcumin in plasma (Cmax) and sevenfold improvement in the area under the concentration-timecurve of curcumin from emu oil formulation compared with pure curcumin. Significant differences were observed in the anti-inflammatory activity of curcumin dry emulsion and plain curcumin. Emu-oil-based formulations showed synergistic anti-inflammatory activity over corn-oil-based formulations with improved photostability. The present study suggests that the dry emulsion may enhance the bioavailability with synergistic anti-inflammatory activity and photostability of curcumin when given orally.

Physicochemical and Pharmacokinetic Evaluation of Praziquantel Co-Crystals by Varying the Spacer Group of Co-Crystal Formers

The research work focuses on investigating the effects of spacer group (varying aliphatic chain length=n) of co-crystal formers (oxalic acid (OA, n=0), (malonic acid (MA, n=1), (succinic acid (SA, n=2), (glutaric acid (GA, n=3), and (adipic acid (AA, n=4) on the physicochemical properties and oral bioavailability of praziquantel (PZQ) co-crystals. For this purpose, different co-crystals of PZQ with dicarboxylic acid co-crystal formers (OA, MA, SA, GA, and AA) were synthesized. These co-crystals were characterized by powder X-ray diffractometry (XRPD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), and thermogravimetry (TG) techniques. The in-vitro (solubility and dissolution) and in-vivo pharmacokinetic (P.K) studies were performed for PZQ co-crystals. Additionally, the effect of polymer hydroxypropyl cellulose (HPC) on the formation of PZQ co-crystals was also investigated. According to the study results, PZQ-SA co-crystal showed improved solubility, dissolution, and oral bioavailability. Overall, the solubility, dissolution, and oral bioavailability are consistent with each other. The order of improved solubility, dissolution, and oral bioavailability is observed as consistent like PZQ-SA &gt; PZQ-AA &gt; PZQ-GA &gt; PZQ-OA &gt; PZQ-MA &gt; pure PZQ. Concerning HPC polymer effects, PZQ-OA, PZQ-MA, PZQ-GA, and PZQ-AA co-crystals were formed successfully in the presence of HPC polymer but the PZQ-SA co-crystal was inhibited.

Cell culture and pharmacokinetic evaluation of a solid dosage formulation containing a water-insoluble orphan drug manufactured by FDM-3DP technology

The in-vitro cytotoxicity, in-vitro permeability and in-vivo pharmacokinetics of a BCS Class-II drug – rufinamide – in a 3DP tablet formulation were evaluated. The cytotoxicity of the 3DP tablet formulation was evaluated with an MTT test; in-vitro permeability was evaluated with a Caco-2 cell culture study; and in-vivo pharmacokinetics were evaluated in Wistar albino male rats. The pharmacokinetic studies were performed following a two-sequence and single-period design approach. The highest Caco-2 permeability was obtained with the 3DP tablet formulation; and the highest cell viability was achieved with the 3DP tablet in both the Hep G2 and Caco-2 cell lines. In the in-vivo pharmacokinetic study, AUC and Cmax values were higher in the 3DP tablet formulation than in the Inovelon® film tablet at a 40 mg/kg dose. Thanks to the increased solubility of the active substance, higher in-vitro permeability and in-vivo absorption were achieved with the 3DP tablet formulation, and with lower cytotoxicity. Based on these promising findings, the 3DP tablet formulation can be considered an effective lower-dose treatment than commercial preparations.