Drug Delivery Letters - Volume 7, Issue 1, 2017

The design and fabrication of transdermal system is an art. Out of many transdermal systems, the introduction of Drug-in-adhesive drug delivery executes close contact of the carrier with stratum corneum to deliver active molecules across the skin and then into the systemic circulation. Thus, aspect of adhesives in transdermal is vital parameter for fabrication design with respect to safety, efficacy and quality of transdermal drug delivery system. Drug-in-adhesive transdermal patch, prevents partial loss of active drug during process involved in manufacturing and drying of the patches. The optimization of the adhesive properties exhibits an important challenge during pharmaceutical development on the side of minimizing the uncertainty of adhesion failure in practice. This article provides groundwork for understanding general properties of pressure sensitive adhesives (PSA) and utilization in the development of transdermal patches. The manuscript summarizes most extensive methods to measure adhesive properties in the time of development studies.

Objective: To formulate pH-sensitive spray dried microspheres loaded with an anti-cancer drug, capecitabine, using hydrolyzed polyacrylamide-grafted-acacia gum (PAAm-g-AG) for colon targeted delivery. Methods: The pH-sensitive PAAm-g-AG was synthesized by free radical polymerization and allowed for alkaline hydrolysis. Results: The obtained microspheres were sphere-shaped and drug encapsulation efficiency was found to be from 76.29% to 97.66%. The dynamic swelling investigation suggested that the PAAm-g-AG attained significant pH-sensitivity property. The in vitro drug release study witnessed that the microspheres prepared with native AG alone were not capable of stopping the drug release within 5 h in stomach and small intestinal pH. But, those microspheres prepared using pH-sensitive PAAm-g-AG having crosslinked with glutaraldehyde (GA), have released small quantity of drug within 5 h, and highest amount of drug was moved to colonic region in a controlled manner up to 24 h. Cross-linking with GA reduced the premature drug release in the pH of stomach and small intestine and also assured most of the drug released in colonic region. We observed an abrupt increase in drug release in the presence of rat caecal contents due to the action of colonic bacteria on PAAm-g-AG polymer.

Objective: The aim of this study was to develop and evaluate self microemulsifying drug delivery system (SMEDDS) to improve oral bioavailability of tacrolimus. Methods: The solubility of tacrolimus in various oils, surfactants and co-surfactants was determined and self-microemulsion preconcentrates were prepared. Pseudo-ternary phase diagrams were constructed to identify stable microemulsion region. The prepared formulations were evaluated for optical clarity, zeta potential, droplet size, viscosity and stability and converted into solid form by the spray drying method and characterized for various parameters. In vitro drug release and pharmacokinetic studies were also carried out to determine the dissolution rate and oral bioavailability. Results: The optimized formulation contained 13.15% w/w of oil phase, 52.21% w/w of Smix and 36.84 % w/w of co-surfactant producing a stable and transparent microemulsion with a percent transmittance, droplet size and zeta potential 99.23%, 52.15 nm and -10.19 mV, respectively. The solid SMEDDS showed colloidal and spherical nature in scanning electron microscopy. X-ray diffraction and differential scanning calorimetry exhibited an amorphous form of drug in solid SMEDDS. In vitro dissolution studies indicated multi folds increase in dissolution rate in liquid and solid SMEDDS as compared to marketed product and API (P < 0.05). Both liquid and solid SMEDDS were stable after three months of storage at different temperature conditions. In vivo pharmacokinetic studies revealed three fold enhanced AUC0-24h, Cmax and Tmax as compared to marketed product (P < 0.05). Conclusion: The results suggested that the prepared SMEDDS formulations could be used as a promising vehicle for improving the solubility and oral bioavailability of tacrolimus.

Background and Objective: Nanoparticles (NPs) have been recognized as important drug delivery agents in several instances including the delivery of antibiotics against intracellular pathogenic microorganisms. In this work the activity of self-assembled nanoparticles (NPs) of clarithromycin (CLA), cationic lipid and polyelectrolytes against important mycobacteria such as Mycobacterium abscessus is evaluated. Methods: NPs from injection of a CLA/cationic lipid ethanol solution in aqueous carboxymethylcellulose (CMC) solution followed or not by the addition of poly (diallyldimethylammonium chloride) (PDDA) to the anionic CLA/cationic lipid/CMC NPs were characterized by dynamic light scattering for sizing, zeta-potential and polydispersity, scanning electron microscopy (SEM) for morphology, colloidal stability along time from sizing and macroscopic observation, inhibitory activity against mycobacteria from determination of minimal inhibitory concentrations (MIC), toxicity against macrophages in culture from determinations of macrophages viability and inhibition of mycobacterial growth in biofilms. Results: Anionic CLA/cationic lipid/CMC NPs incorporated higher percentage of CLA than the cationic CLA/cationic lipid/CMC/PDDA NPs and showed higher antimicrobial activity against M. abscessus and lower toxicity to macrophages than the cationic NPs. Conclusion: These findings opened the possibility of extending the incorporation of other lipophilic antibiotics or drugs into the here described self-assembled NPs and showed NPs adequacy to deliver antibiotics and drugs intracellularly for sustained release inside cells and activity against biofilms growth.

Context: Nitrendipine is a model drug which is widely used to treat hypertension. It has very low solubility in water so, it has been formulated in various dosage forms to improve the dissolution. Further, it has high first pass metabolism and bioavailability is very less. Objective: The present study gives the preparation and characterization of nitrendipine nanoliposome for controlled delivery. Materials & Methods: The vesicles were made up of phosphatidylcholine, cholesterol and dicetyl phosphate using thin lipid film hydration method for varying lipid ratio. The Nanoliposomes were characterized for size distribution, entrapment efficiency and charge characteristics. In vitro drug release profile and ex-vivo dermal permeation tests were carried out on prepared Nanoliposomes. Results & Discussion: The vesicle size ranges from 211-235 nm with the entrapment efficiencies from 36-59%. Polydispersity indices were from 0.331-0.372 and zeta potential was - 61 to -66 mV. When formulations were compared with carbopol gel, NLG-5 showed controlled drug release patterns. In ex vivo drug permeation, NLG-5 showed maximum drug permeation with flux 0.622 μg/cm2 and distribution parameter 7.177 cm2 /hr. Conclusion: The results indicate that prepared liposome has optimum physical characters and provide adequate drug delivery thereby reducing the wastage of drug.

Background and Objective: Meclizine (MCZ) is a Biopharmaceutical Classification System (BCS) class-II drug, which is a poorly water-soluble drug along-with very slow-onset of action. In this study MCZ was complexed with different cyclodextrins (CDs), like, sodium sulfobutylether β-CD (SBEβCD), hydroxypropyl β-CD, randomly methylated β-CD, and methyl β-CD, to enhance its solubility for repurposing of this drug for the treatment of infectious diseases and cancer. Methods: Phase solubility experiments were performed to determine the pattern of MCZ solubilization. Characterization of MCZ-CD complexes were done by Fourier transform infrared (FTIR), X-ray powder diffraction analysis (XRPD) and differential scanning calorimetry (DSC). Results: The FTIR, XRPD and DSC studies clearly revealed the formation of inclusion complexes between MCZ and CDs. Phase solubility results showed that MCZ solubility increased linearly with CD at lower concentration, then get saturated in higher concentration, indicative of an AN type solubility profile. Aqueous solubility of MCZ was enhanced upto 8-16 folds through CD inclusion complexation. Conclusion: These complexation studies confirms the results of molecular modeling in which hydroxy and methyl-substituted CDs revealed the higher inclusion as compared with sulfobutyl substituted CDs.

Background and Objective: The 4T1 murine breast cancer cell line is commonly employed to study breast cancer metastasis. Transfections to this cell line are frequently carried out using lipid/polymer based gene delivery vehicles. The research paper attempts to use peptide based transfecting agents Str-R8 and MTS-AR8 for in vitro transfection of 4T1 cells. Methods: These peptides were investigated previously by the authors and showed comparable plasmid DNA complexation abilities. The efficiency of Str-R8, MTS-AR8 in delivery of the plasmid DNA, pSFCMV- SEAP to 4T1 cells is compared to the cationic lipid reagent Lipofectamine®3000. Transfection was measured by estimating the ability of the expressed reporter gene i.e., secreted alkaline phophatase to cleave the substrate para-Nitrophenylphosphate to para-Nitrophenol. Results: Transfection of 4T1 by MTS-AR8/pSF-CMV-SEAP was twofold greater than that mediated by Str-R8/pSF-CMV-SEAP (probability of the values being similar; p<0.05) and comparable to Lipofectamine ®3000/pSF-CMV-SEAP (probability of the values being similar; p>0.5) at a peptide basic amino acid per nucleic acid phosphate ratio of 5:1. Increasing the peptide basic amino acid per nucleic acid phosphate ratio, of MTS-AR8 resulted in a decrease in the transfection of 4T1 cells (probability of the obtained values being similar; p <0.06). Conclusion: The MTS-AR8 peptide has potential and can be further investigated for nucleic acid delivery involving the 4T1 cell line.