Preparation of Tamsulosin Hydrochloride-Loaded Mucoadhesive In Situ Gelling Polymeric Formulation for Nasal Delivery in Geriatrics.

This study aimed to prepare tamsulosin hydrochloride (HCl)-loaded in situ gelling formulation by using hydroxypropyl methylcellulose (HPMC), gellan gum, poloxamer 188, and benzalkonium chloride. Physicochemical evaluation of formulations included determination of pH, viscosity, gelation time, gel strength, drug content, and sterility. In silico study was performed to analyze interactions between polymers, drug, and mucin glycoprotein. In vitro degradation time, drug release, ex vivo mucoadhesion time, permeation, in vivo pharmacokinetics, and stability studies were performed to assess the formulation. Formulations were transparent and displayed acceptable physicochemical attributes. Tamsulosin HCl and polymers interacted via non-covalent interactions. HPMC formed hydrogen bonds, hydrophobic and van der Waals interactions with mucin protein while the drug formed hydrogen bonds only. Gel formulation degraded in simulated nasal fluid within 24 h. In situ gelling formulation showed 83.8 ± 1.7% drug release and remained adhered to the mucosa for 24.5 ± 1 h. A higher (~ 1.85 times) drug permeation was recorded through mucosa within 6 h by in situ gelling formulation when compared to control counterparts (aqueous solution of drug and in situ gelling formulation without poloxamer 188). Nasal administration of tamsulosin HCl by using in situ gelling formulation led to a ~ 3.3 and ~ 3.5 times, respectively, higher Cmax (maximum plasma concentration) and AUCtotal (total area under the curve) than the orally administered aqueous solution. Relative bioavailability of drug delivered by nasal in situ gelling formulation was 3.5 times the oral counterpart. These results indicated that the prepared in situ gelling formulation can act as a promising candidate for systemic administration of tamsulosin HCl.

Design and Evaluation of Hydrophobic Ion Paired Insulin Loaded Self Micro-Emulsifying Drug Delivery System for Oral Delivery.

Despite several novel and innovative approaches, clinical translation of oral insulin delivery into commercially viable treatment is still challenging due to its poor absorption and rapid degradation in GIT. Thus, an insulin-SDS hydrophobic ion pair loaded self-microemulsifying drug delivery system (SMEDDS) was formulated to exploit the hypoglycemic effects of orally delivered insulin. Insulin was initially hydrophobically ion paired with sodium dodecyl sulphate (SDS) to enhance its lipophilicity. The successful complexation of Insulin-SDS was confirmed by FTIR and surface morphology was evaluated using SEM. Stability of insulin after its release from HIP complex was evaluated using SDS PAGE. Subsequently, Ins-SDS loaded SMEDDS was optimized using two factorial designs. In vitro stability of insulin entrapped in optimized SMEDDS against proteolytic degradation was also assessed. Further, antidiabetic activity of optimized Ins-SDS loaded SMEDDS was evaluated in diabetic rats. Insulin complexed with SDS at 6:1 (SDS/insulin) molar ratio with almost five-fold increased lipophilicity. The SMEDDS was optimized at 10% Labraphil M2125 CS, 70% Cremophore EL, and 20% Transcutol HP with better proteolytic stability and oral antidiabetic activity. An Ins-SDS loaded SMEDDS was successfully optimized. Compared with insulin and Ins-SDS complex, the optimized SMEDDS displayed considerable resistance to GI enzymes. Thus, the SMEDDS showed potential for effective delivery of macromolecular drugs with improved oral bioavailability.

Fabrication and Characterization of Celecoxib-Loaded Chitosan/Guar Gum-Based Hydrogel Beads.

The aim of this study was to fabricate celecoxib-loaded chitosan/guar gum (CS/GG) single (SC) and dual (DC) crosslinked hydrogel beads using the ionotropic gelation approach. The prepared formulations were evaluated for entrapment efficiency (EE%), loading efficiency (LE%), particle size and swelling studies. The performance efficiency was assessed by in vitro drug release, ex-vivo mucoadhesion, permeability, ex-in vivo swelling and in vivo anti-inflammatory studies. The EE% was found to be ~55% and ~44% for SC5 and DC5 beads, respectively. The LE% was ~11% and ~7% for SC5 and DC5 beads, respectively. The beads showed a matrix-like network with thick fibers. The particle size of beads ranged from ~2.74 to 1.91 mm. About 74% and 24% celecoxib was released from SC and DC hydrogel beads, respectively, within 24 h. The SC formulation showed higher %swelling and permeability than the DC counterpart, while the %mucoadhesion was relatively higher for DC beads. During the in vivo study, a significant decrease in the inflammation of the rat paw and inflammatory markers including C-reactive proteins (CRP) and interleukin-6 (IL-6) was observed following treatment with the prepared hydrogel beads; however, the SC formulation showed better therapeutic efficiency. In conclusion, celecoxib-loaded crosslinked CS/GG hydrogel beads can provide sustained drug release and act as potential candidates for managing inflammatory conditions.

Corrigendum to "The effective transfection of a low dose of negatively charged drug-loaded DNA-nanocarriers into cancer cells via scavenger receptors"[Journal of Pharmaceutical Analysis volume 11 (2021) 174-182].

[This corrects the article DOI: 10.1016/j.jpha.2020.10.003.].

Analgesic and Anti-Inflammatory Properties of Two Hydrogel Formulations Comprising Polyherbal Extract.

Background: Nature represents a basic source of medicinal scaffolds that can develop into potent drugs used in the treatment of many diseases. Aim: The present study was planned to evaluate the combined effects of polyherbal methanolic extract of the herbs (fruit of capsicum, bark of cinnamon, rhizome of turmeric and rhizome of ginger) that were individually well known for their analgesic and anti-inflammatory activities. Furthermore, we aimed to develop hydrogel formulation of this polyherbal extract and to characterize and evaluate its analgesic and anti-inflammatory potential. Materials and Methods: Zingiber officinale (R.), Capsicum annuum (L.), Curcuma longa (L.), and Cinnamomum verum (J.) polyherbal extract (GCTC) was prepared by maceration and evaluated for analgesic and anti-inflammatory potential. Then, two different types of hydrogel formulation were prepared. One is pH-based hydrogel in which carbopol-940 was used and the other is temperature-based gel in which methocel-K100 was used as gelling agent. Different concentrations of polyherbal extract (GCTC), at 1%, 3% and 5%, were used in hydrogel formulation. These prepared hydrogel formulations were characterized and evaluated for analgesic and anti-inflammatory potential. Results: Results show that polyherbal extract and all the developed formulations of polyherbal extract (GCTC), at concentrations of 1%, 3% and 5%, have significant analgesic and anti-inflammatory effects with good appearance, homogeneity, spreadability, extrudability and stability. Conclusion: It was concluded from this project that polyherbal extract (GCTC) and its hydrogel have significant analgesic and anti-inflammatory potential.

Design and Characterization of Agarose/HPMC Buccal Films Bearing Ondansetron HCl In Vitro and In Vivo: Enhancement Using Iontophoretic and Chemical Approaches.

The study was aimed at designing and characterizing the ondansetron hydrochloride (OND) bearing agarose (AG), and hydroxypropyl methyl cellulose (HPMC) mucoadhesive buccal films employing glycerol as a plasticizer. The buccal delivery of ondansetron hydrochloride was remarkably boosted by employing physical (iontophoresis) and chemical enhancement approaches (chemical penetration enhancers). To explore the influence of different formulation components, i.e., agarose, hydroxypropyl methyl cellulose (HPMC), and glycerol on various evaluating parameters, i.e., tensile strength, swelling index, ex vivo mucoadhesion time, and subsequently on in vitro drug release, a D-optimal design was opted. A buccal film bearing OND was mounted on bovine buccal mucosa for ex vivo permeation studies and impact of chemical and physical enhancement techniques on the permeation profile was also analysed. A linear release profile was revealed in in vitro drug release of OND over 60 minutes and outcomes ascertained the direct relationship between HPMC content and in vitro drug release and inverse relationship was depicted by AG content. The FTIR and DSC thermal analysis was executed to determine the physicochemical interactions and results exposed no chemical interactions between drug and polymers. The drug (OND) appeared as tiny crystals on smooth film surface during scanning electron microscopy (SEM) analysis. A notable enhancement in permeation flux, i.e., 761.02 µg/min of OND during ex vivo permeation studies was witnessed after the application of current (0.5-1 mA) without any time lag and with enhancement ratio of 3.107. A time lag of 15 minutes, 19 minutes, and 26 minutes with permeation flux of 475.34 µg/min, 399.35 µg/min, and 244.81 µg/min was observed after chemical enhancer pretreatment with propylene glycol, Tween 80, and passive, respectively. Rabbit was employed as the experimental animal for pharmacokinetic studies (in vivo) and cats for pharmacological activity (in vivo), and the results illustrated the enhanced bioavailablity (2.88 times) in the iontophoresis animal group when compared with the rabbits of control group. Likewise, a remarkable reduction in emesis events was recorded in cats of iontophoresis group. Conclusively, the histopathological examinations on excised buccal mucosa unveiled no severe necrotic or cytopathetic outcomes of current.

Controlled release floating drug delivery system for proton pump inhibitors lansoprazole: In-vitro, In-vivo floating and pharmacokinetic evaluation.

Lansoprazole (LPZ) show poor bioavailability because of first pass effect and absorption factors. The floating delivery systems could reduce fluctuations in plasma drug concentration through maintaining desirable plasma drug concentration. The objective of present study was to enhance bioavailability despite first pass effect through continuous availability of drug from floating system. Gum tragacanth (GT) and itaconic acid (IA) based floating hydrogels (FH) were synthesized. Parameters optimized were; microwave radiation exposure time, pH, GT:IA ratio and concentration of the glutaraldehyde. Optimized FH were evaluated for entrapment efficiency (% EE), in-vitro release, FTIR, SEM, and in- vitro and in-vivo floating study. Finally, pharmacokinetic was evaluated in ulcer-induced SD rats. Grafting percentage, swelling ratio and %EE of LPZ was 115%, Ì´250% and 90%, respectively. Microwave radiation exposure time, pH of reaction medium, GT:IA ratios and cross linker concentration were 2 min, pH 5, ratios 2:1 and 0.02%, respectively. The optimized FH showed acceptable floating behavior. The X-ray images revealed that hydrogels remained floated over gastric contents up to 24 hours. The in-vitro release and pharmacokinetics revealed availability of LPZ upto to 24h in-vitro and in ulcer-induced SD rats, respectively. The present hydrogels based floating system of lansoprazole is capable to extend the gastric residence time upto 24 hours.

Evaluation of sustained-release in-situ injectable gels, containing naproxen sodium, using in vitro, in silico and in vivo analysis.

The study aimed to fabricate naproxen sodium loaded in-situ gels of sodium alginate. Different in-situ gel forming solutions of naproxen sodium and sodium alginate were prepared and gel formation was studied in different physiological ions i.e., CaCl2 and Ca-gluconate. The prepared gel formulations were evaluated for different physical attributes such as gelation time, sol-gel fraction, ATR-FTIR spectroscopy and in silico molecular dynamics (MD) simulations. Drug release studies were carried out in a dialysis membrane using USP dissolution basket apparatus-I. In vivo anti-inflammatory studies were performed in Sprague-Dawley rats having carrageenan-induced hind paw inflammation. Higher polymer concentration in formulations resulted in decreased gelation time and an increased gel fraction. The ATR-FTIR and MD simulation revealed H-bonding between the alginate and naproxen sodium at 3500-3200 cm-1 with a RMSD of ∼2.8 Å and binding free energy ΔGpred (GB) = -10.93 kcal/mol. In vitro drug release studies from F8CAG suggested a sustained release of naproxen sodium. In vivo studies revealed a continuous decrease in swelling degree (≈-5.28 ± 0.210 mm) in inflamed hind paw of Sprague-Dawley rats over 96 h. The in-situ gel forming injectable preparation (F8CAG) offers a sustained release of naproxen sodium in the articular cavity which promises the treatment of chronic inflammatory conditions such as arthritis.

Formulation, Optimization, in vitro and in-vivo evaluation of levofloxacin hemihydrate Floating Tablets

Abstract The objective of the present investigation was to design, optimize and characterize the gastro retentive floating levofloxacin tablets and perform in-vivo evaluation using radiographic imaging. The floating tablets were prepared by using polymers i.e hydroxy propyl methyl cellulose (HPMC-K4M) and carbopol-940 individually and in combination by nonaquous granulation method. All the Formulations were evaluated for swelling index (S.I), floating behavior and in-vitro drug release kinetics. The compatibility study of levofloxacin with other polymers was investigated by FTIR, DSC, TGA and XRD. Results from FTIR and DSC revealed no chemical interaction amongst the formulation components. The optimized formulation (F11) showed floating lag time (FLT), total floating time (TFT) swelling index (S.I) of 60 sec, >16h and approximately 75 %, respectively. Moreover, F11 showed zero order levofloxacin release in simulated gastric fluid over the period of 6 h. X-ray studies showed that total buoyancy time was able to delay the gastric emptying of levofloxacin floating tablets in rabbits for more than 4 hours. In conclusion the optimized formulation (F11) can be used for the sustained delivery of levofloxacin for the treatment of peptic ulcer.

Fabrication and Biological Assessment of Antidiabetic α-Mangostin Loaded Nanosponges: In Vitro, In Vivo, and In Silico Studies.

Type 2 diabetes mellitus has been a major health issue with increasing morbidity and mortality due to macrovascular and microvascular complications. The urgent need for improved methods to control hyperglycemic complications reiterates the development of innovative preventive and therapeutic treatment strategies. In this perspective, xanthone compounds in the pericarp of the mangosteen fruit, especially α-mangostin (MGN), have been recognized to restore damaged pancreatic ß-cells for optimal insulin release. Therefore, taking advantage of the robust use of nanotechnology for targeted drug delivery, we herein report the preparation of MGN loaded nanosponges for anti-diabetic therapeutic applications. The nanosponges were prepared by quasi-emulsion solvent evaporation method. Physico-chemical characterization of formulated nanosponges with satisfactory outcomes was performed with Fourier transform infra-red (FTIR) spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Zeta potential, hydrodynamic diameter, entrapment efficiency, drug release properties, and stability studies at stress conditions were also tested. Molecular docking analysis revealed significant interactions of α-glucosidase and MGN in a protein-ligand complex. The maximum inhibition by nanosponges against α-glucosidase was observed to be 0.9352 ± 0.0856 µM, 3.11-fold higher than acarbose. In vivo studies were conducted on diabetic rats and plasma glucose levels were estimated by HPLC. Collectively, our findings suggest that MGN-loaded nanosponges may be beneficial in the treatment of diabetes since they prolong the antidiabetic response in plasma and improve patient compliance by slowly releasing MGN and requiring less frequent doses, respectively.

Microneedle based transcutaneous delivery of low molecular weight heparin.

This study aimed to fabricate and characterize polymeric microneedle patches for rapid and non-invasive administration of enoxaparin across skin layers. The patches comprising of PVA, sorbitol and enoxaparin sodium were prepared by employing micromolding technique. Formulated patches were characterized physicochemically by folding endurance, dimensional analysis and swelling study, morphologically by optical and scanning electron microscopy and thermally by thermogravimetric analysis. Moreover, performance efficiency of prepared polymeric device was analyzed by in-vitro drug release study and piercing ability. Prepared patches showed appropriate dimensions and folding endurance (i.e., ~1100) indicating satisfactory integrity of polymeric device. Patches exhibited appropriately distanced needles with pointed tips in optical and scanning electron microscopy analysis. Thermogravimetric analysis proved thermal stability of formulation ingredients and prepared patches. Swelling percentage was >110 % suggesting that prepared formulation would allow penetration of physiological fluids in its polymeric network. Maximum (~89%) drug was released within ~2 hours during in-vitro release study. In-vitro piercing ability experiments suggested that prepared patches successfully breached skin barrier stratum corneum. It is concluded that prepared microneedle device can serve as a potential alternative of currently employed invasive parenteral route for rapid and efficient administration of enoxaparin sodium in the systemic circulation.

The effective transfection of a low dose of negatively charged drug-loaded DNA-nanocarriers into cancer cells via scavenger receptors.

DNA-nanotechnology-based nano-architecture scaffolds based on circular strands were designed in the form of DNA-nanowires (DNA-NWs) as a polymer of DNA-triangles. Circularizing a scaffold strand (84-NT) was the critical step followed by annealing with various staple strands to make stiff DNA-triangles. Atomic force microcopy (AFM), native polyacrylamide gel electrophoresis (PAGE), UV-analysis, MTT-assay, flow cytometry, and confocal imaging were performed to assess the formulated DNA-NWs and cisplatin (CPT) loading. The AFM and confocal microscopy images revealed a uniform shape and size distribution of the DNA-NWs, with lengths ranging from 2 to 4 µm and diameters ranging from 150 to 300 nm. One sharp band at the top of the lane (500 bp level) with the loss of electrophoretic mobility during the PAGE (native) gel analysis revealed the successful fabrication of DNA-NWs. The loading efficiency of CPT ranged from 66.85% to 97.35%. MTT and flow cytometry results showed biocompatibility of the blank DNA-NWs even at 95% concentration compared with the CPT-loaded DNA-NWs. The CPT-loaded DNA-NWs exhibited enhanced apoptosis (22%) compared to the apoptosis (7%) induced by the blank DNA-NWs. The release of CPT from the DNA-NWs was sustained at < 75% for 6 h in the presence of serum, demonstrating suitability for systemic applications. The IC50 of CPT@DNA-NWs was reduced to 12.8 nM CPT, as compared with the free CPT solution exhibiting an IC50 of 51.2 nM. Confocal imaging revealed the targetability, surface binding, and slow internalization of the DNA-NWs in the scavenger-receptor-rich cancer cell line (HepG2) compared with the control cell line.

Ibuprofen-loaded centrifugally spun microfibers for quick relief of inflammation in rats.

The conventional dosage forms (tablets, capsules) of ibuprofen have less potential in the suppression of pain and inflammation due to their slow dissolution rates and lower bioavailability. The aim of this study was to fabricate fibrous solid dispersion of ibuprofen for improved dissolution rate and quick therapeutic action. Drug-loaded microfibers were fabricated using centrifugal melt spinning (CMS) technique from the physical mixture of sucrose, ibuprofen and a hydrophilic polymer, PVP. These fibers were characterized by SEM, PXRD, DSC, and FTIR spectroscopy. The selected formulation was also pressed into tablets by direct compression method followed by its in vitro and in vivo characterization. The production yield of fibers was 75 ± 2% with an average diameter of 15 ± 5 µm. The drug loading efficiency (DLE) was 85 ± 5%. The tablets dissolved rapidly (<40 s). In vitro dissolution studies have shown >85% of ibuprofen dissolved from tablet within first 2 min which was ∼5 times quicker than drug alone. Dissolution efficiency has improved from 0.63 of ibuprofen to 0.95 of that in fibers with ∼7 times reduction in mean dissolution time. PXRD, and DSC have shown the amorphous state of ibuprofen in the formulation and FTIR spectra demonstrated no interaction of drug with excipients. In vivo anti-inflammatory studies using rabbits revealed a significant (p < 0.05) reduction in paw volume (mm) in the groups treated with fibrous formulation. This study concludes that microfibers produced by centrifugal melt spinning have improved dissolution rates and bioavailability of ibuprofen. Incorporation of polymer in the formulations improves the production yield and drug loading efficiency of microfibers.

The integrin facilitated internalization of fibronectin-functionalized camptothecin-loaded DNA-nanofibers for high-efficiency anticancer effects.

Camptothecin (CMPT) in a free form is extremely cytotoxic as well as hydrophobic drug, and is considered to be highly contagious for systemic administration. The fibronectin (FN)-functionalized DNA-based nanocarrier has been designed to load CMPT and target integrin (αvß3) receptors which are highly expressed on the A549 cancer cells. Here, we report DNA nanocarrier in the form of DNA-nanofibers (DNA-NFs) capable of loading CMPT via strand intercalation in the GC (base pairs)-rich regions of the DNA duplex. Hence, our keen purpose was to explore the potential of DNA-NFs to load CMPT and assess the improvements of the outcomes in terms of enhanced therapeutic effects to integrin-rich A549 cancer cells with reduced cytotoxic effects to integrin-lacking HEK293 cells. DNA-NFs were formulated as a polymer of DNA triangles. DNA triangles arranged in a programmed way through the complementary overhangs present at the vertices. DNA triangles were primarily obtained through the annealing of the freshly circularized scaffold strands with the three distinct staple strands of specific sequences. The polymerized triangular tiles instead of forming two-dimensional nanosheets underwent self-coiling to give rise to DNA-NF-shaped structures. Flow cytometry and MTT assays were performed to observe cytotoxic and apoptotic effects on integrin-rich A549 cancer cells compared with the integrin-deficient HEK293 cells. AFM, native-page, and confocal experiments confirmed the polymerization of DNA triangles and the morphology of the resulting nanostructures. AFM and confocal images revealed the length of DNA-NFs to be 3-6 µm and the width from 70 to 110 nm. CMPT loading (via strands intercalation) in GC-rich regions of DNA-NFs and the FN functionalization (TAMRA tagged; red fluorescence) via amide chemistry using amino-modified strands of DNA-NFs were confirmed through the UV-shift analysis (> 10 nm shift) and confocal imaging. Blank DNA-NFs were found to be highly biocompatible in 2-640 µM concentrations. MTT assay and flow cytometry experiments revealed that CMPT-loaded DNA-NFs showed a dose-dependent decrease in the cell viability to integrin-rich A549 cancer cells compared with the integrin-deficient HEK293 cells. Conclusively, FN-functionalized, CMPT-loaded DNA-NFs effectively destroyed integrin-rich A549 cancer cells in a targeted manner compared with integrin-deficient HEK293 cells. Grapical abstract.

Personalised 3D Printed Fast-Dissolving Tablets for Managing Hypertensive Crisis: In-Vitro/In-Vivo Studies.

Hypertensive crisis (HC) is an emergency health condition which requires an effective management strategy. Over the years, various researchers have developed captopril based fast-dissolving formulations to manage HC; however, primarily, the question of personalisation remains unaddressed. Moreover, commercially these formulations are available as in fixed-dose combinations or strengths, so the titration of dose according to patient's prerequisite is challenging to achieve. The recent emergence of 3D printing technologies has given pharmaceutical scientists a way forward to develop personalised medicines keeping in view patients individual needs. The current project, therefore, is aimed at addressing the limitations as mentioned above by developing fast-dissolving captopril tablets using 3D printing approach. Captopril unloaded (F1) and loaded (F2-F4) filaments were successfully produced with an acceptable drug loading and mechanical properties. Various captopril formulations (F2-F4) were successfully printed using fused deposition modelling technique. The results revealed that the formulations (F2 and F3) containing superdisintegrant had a faster extent of dissolution and in-vivo findings were endorsing these results. The present study has successfully exhibited the utilisation of additive manufacturing approach to mend the gap of personalisation and manufacturing fast-dissolving captopril 3D printed tablets. The procedure adopted in the present study may be used for the development of fused deposition modelling (FDM) based fast-dissolving 3D printed tablets.

Self-assembled insulin and nanogels polyelectrolyte complex (Ins/NGs-PEC) for oral insulin delivery: characterization, lyophilization and in-vivo evaluation.

Introduction: Insulin is given by injection, because when administered orally, it would be destroyed by enzymes in the digestive system, hence only about 0.1% reaches blood circulation. The purpose of the present study was to use pH sensitive polyelectrolyte methyl methacrylate (MMA)/itaconic acid (IA) nanogels as carriers in an attempt to improve absorption of insulin administered orally. Methods: Insulin (Ins) was incorporated into the MMA/IA nanogels (NGs) using the polyelectrolyte complexation (PEC) method to form Ins/NGs-PEC. Several parameters, including Ins:NGs ratio, pH, incubation time and stirring rate were optimized during preparation of InsNGs-PEC. The prepared formulations were characterized in terms of particle size (PS), polydispersity index (PdI), zeta potential (ZP) and percent entrapment efficiency (% EE). Results: The optimized InF12 nanogels had a PS, PdI, ZP and %EE of 190.43 nm, 0.186, -16.70 mV and 85.20%, respectively. The InF12 nanogels were lyophilized in the presence of different concentrations of trehalose as cryoprotectant. The lyophilized InF12 containing 2%w/v trahalose (InF12-Tre2 nanogels) was chosen as final formulation which had a PS, PdI, ZP and %EE of 430.50 nm, 0.588, -16.50 mv and 82.10, respectively. The in vitro release of insulin from InF12-Tre2 nanogels in the SGF and SIF were 28.71% and 96.53%, respectively. The stability study conducted at 5±3°C for 3 months showed that lnF12-Tre2 nanogels were stable. The SDS-PAGE assay indicated that the primary structure of insulin in the lnF12-Tre2 nanogels was intact. The in-vivo study in the diabetic rats following oral administration of InF12-Tre2 nanogels at a dose of 100 IU/kg body weight reduced blood glucose level significantly to 51.10% after 6 hours compared to the control groups. Conclusions: The pH sensitive MMA/IA nanogels are potential carriers for oral delivery of insulin as they enhanced the absorption of the drug.

Freeze-Dried Lopinavir-Loaded Nanostructured Lipid Carriers for Enhanced Cellular Uptake and Bioavailability: Statistical Optimization, in Vitro and in Vivo Evaluations.

Nanostructured lipid carriers (NLCs) loaded with lopinavir (LPV) were prepared by the high-shear homogenization method. The LPV-NLCs formulations were freeze-dried using trehalose as a cryoprotectant. In vitro release studies in simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8) showed a burst release. The optimized freeze-dried formulation (LPV-NLC-7-Tres) had a particle size (PS), polydispersity index (PdI), zeta potential (ZP) and % entrapment efficiency (%EE) of 286.8 ± 1.3 nm, 0.413 ± 0.017, -48.6 ± 0.89 mV and 88.31 ± 2.04%, respectively. The optimized formulation observed by transmission and scanning electron microscopes showed a spherical shape. Differential scanning calorimetry study revealed the absence of chemical interaction between the drug and lipids. In vitro cellular uptake study using Caco-2 cell line showed a higher LPV uptake from LPV-NLC-7-Tres formulation compared to the free LPV-suspension. The 6-month stability study showed a minimum rise of ~40 nm in PS, while no significant changes in PdI, ZP and drug content of the LPV-NLC-7-Tres formulation stored at 5 °C ± 3 °C. The bioavailability of LPV following oral administration of LPV-NLC-7-Tres in male Wistar rats was found 6.98-fold higher than the LPV-suspension. In conclusion, the nanostructure lipid carriers are potential carriers for improving the oral bioavailability of lopinavir.

RP-HPLC based method for the determination of Tamsulosin HCl in API, Prepared dosage form and spiked plasma.

An analytical method for measurement of tamsulosin HCl from its different life cycle stages was developed using RP-HPLC technique. The elution of tamsulsoin was studied using MediterraneaTM Sea 18 column (dimesions 250 × 4.6 mm and pore size 5µm) and mobile phase comprising of buffer (pH 5.4): Acetonitrile (ACN) at ratio 60:40. The tamsolusin HCl elution was also studied by varying the operating conditions including the composition and flow rate of mobile phase, stationary phase temperature and scanning wavelength. The optimal elution conditions include; a) mobile phase flow rate; 1ml/min, b) wavelength; 224nm and stationary phase temperature 30°C. Linearity was recorded in the absorption data over tamsulosin concentration range of 0.007 to 40µg/ml. The values of paramters LOD and LOQ noted for tamsulosin dissolved in mobile phase were 0.0014 and 0.042µg/ml respectively, while for the counterpart in spiked plasma were 0.0017 and 0.051µg/ml respectively. The analytical method was prompt, accurate, reproducible and suitable for analysis of tamsulosin HCl in different samples of interest at formulation, regulation and clinical evaluations.

Advanced drug delivery to the lymphatic system: lipid-based nanoformulations.

The delivery of drugs and bioactive compounds via the lymphatic system is complex and dependent on the physiological uniqueness of the system. The lymphatic route plays an important role in transporting extracellular fluid to maintain homeostasis and in transferring immune cells to injury sites, and is able to avoid first-pass metabolism, thus acting as a bypass route for compounds with lower bioavailability, ie, those undergoing more hepatic metabolism. The lymphatic route also provides an option for the delivery of therapeutic molecules, such as drugs to treat cancer and human immunodeficiency virus, which can travel through the lymphatic system. Lymphatic imaging is useful in evaluating disease states and treatment plans for progressive diseases of the lymph system. Novel lipid-based nanoformulations, such as solid lipid nanoparticles and nanostructured lipid carriers, have unique characteristics that make them promising candidates for lymphatic delivery. These formulations are superior to colloidal carrier systems because they have controlled release properties and provide better chemical stability for drug molecules. However, multiple factors regulate the lymphatic delivery of drugs. Prior to lymphatic uptake, lipid-based nanoformulations are required to undergo interstitial hindrance that modulates drug delivery. Therefore, uptake and distribution of lipid-based nanoformulations by the lymphatic system depends on factors such as particle size, surface charge, molecular weight, and hydrophobicity. Types of lipid and concentration of the emulsifier are also important factors affecting drug delivery via the lymphatic system. All of these factors can cause changes in intermolecular interactions between the lipid nanoparticle matrix and the incorporated drug, which in turn affects uptake of drug into the lymphatic system. Two lipid-based nanoformulations, ie, solid lipid nanoparticles and nanostructured lipid carriers, have been administered via multiple routes (subcutaneous, pulmonary, and intestinal) for targeting of the lymphatic system. This paper provides a detailed review of novel lipid-based nanoformulations and their lymphatic delivery via different routes, as well as the in vivo and in vitro models used to study drug transport in the lymphatic system. Physicochemical properties that influence lymphatic delivery as well as the advantages of lipid-based nanoformulations for lymphatic delivery are also discussed.

Swelling and aspirin release study: cross-linked pH-sensitive vinyl acetate-co-acrylic acid (VAC-co-AA) hydrogels.

The objective of this work was to develop new pH-sensitive hydrogels to deliver gastric mucosal irritating drugs to the lower part of the gastrointestinal tract. For this purpose, cross-linked vinyl acetate-co-acrylic acid (VAC-co-AA) hydrogels were synthesized by using N, N, methylene bisacrylamide (MBAAm) as a cross-linking agent. Different ratios of 90:10, 70:30, 50:50, 30:70, and 10:90 of VAC-co-AA were synthesized. All of the compositions were cross-linked using 0.15, 0.30, 0.45, and 0.60 mol percent MBAAm. Swelling and aspirin release were studied for 8 hour period. The drug release data were fitted into various kinetic models like the zero-order, first-order, Higuchi, and Peppas. Hydrogels were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. In addition to the above, these hydrogels were loaded with 2%, 8% and 14% w/v aspirin solutions, keeping the monomeric composition and degree of cross-linking constant. In conclusion, it can be said that aspirin can be successfully incorporated into cross-linked VAC/AA hydrogels and its swelling and drug release can be modulated by changing the mole fraction of the acid component in the gels.