Ibuprofen Syrup Made by Mixed Solubilization Technique: Formulation and Evaluation

The aim of the present study was to prepare a liquid dosage form (syrup) of a NSAID (ibuprofen) by mixed solvency technique. The syrup formulation was prepared by using mixed hydrotropic method in which potassium citrate, sodium citrate, potassium acetate and disodium hydrogen phospahte were used as hydrotropes. Glycerine and tween 80 were also used in the formulation. The syrup was prepared by agitation method. At first solubility of the model drug Ibuprofen was identified by dissolving it with different hydrotropes. It was observed that the solubility of ibuprofen increased with increase in concentration of the hydrotropes. However, it is difficult to develop a formulation with very concentration of hydrotropes. Therefore, co-solvent and surfactants were also added to enhance the solubility of the ibuprofen. Glycerine and tween 80 were used along with blends of hydrotropes to increase the solubility of Ibuprofen. The results, showed 3000 times increase in solubility of the ibuprofen drug. Also, the drug content of the prepared formulation was found to be 99.67% which proved the mixed solubilizing technique as a efficient and stable method for development of pharmaceutical dosage forms

Statistical Optimization of Oxidative Derivatization of Polyethylene Glycol to Polyethylene Carboxylate Using Custom Design Approach

Reaction optimization has been a tedious task for the research chemist for very long and many approaches has been employed to achieve the best reaction condition resulting in highest yield. As an answer to this problem the statistical optimization approach has better chances of providing most acceptable solution to it. Through, our present work we have found that among other statistical approaches the custom design approach is the best methodology to be adopted for optimizing any synthetic reaction. The oxidative transformation of polyethylene glycol into polyethylene carboxylate by the use of TEMPO, NaClO and KBr; has been optimized by identifying the key factors affecting the yield and exact ratios of them to achieve highest possible yield. Here, we have employed custom design approach to further limit the experimental runs and yet find a better possible combination of reagents and conditions to get highest yield with maximum purity. This method has reduced the number of runs to only 16, which was 1024 in case of the traditional OVAT approach and in full factorial approach it was 64 runs. Thus, custom design method of DoE has been satisfactorily utilized for optimizing the oxidative derivatization of polyethylene glycol to polyethylene carboxylate

Mechanistic Insight into Receptor-Mediated Delivery of Cationic-β-Cyclodextrin:Hyaluronic Acid-Adamantamethamidyl Host:Guest pDNA Nanoparticles to CD44⁺ Cells

Targeted delivery is a key element for improving the efficiency and safety of nonviral vectors for gene therapy. We have recently developed a CD44 receptor targeted, hyaluronic acid-adamantamethamidyl based pendant polymer system (HA-Ad), capable of forming complexes with cationic β-cyclodextrins (CD-PEI⁺) and pDNA. Complexes formed using these compounds (HA-Ad:CD-PEI⁺:pDNA) display high water solubility, good transfection efficiency, and low cytotoxicity. Spatial and dynamic tracking of the transfection complexes by confocal microscopy and multicolor flow cytometry techniques was used to evaluate the target specificity, subcellular localization, and endosomal escape process. Our data shows that cells expressing the CD44 receptor undergo enhanced cellular uptake and transfection efficiency with HA-Ad:CD-PEI⁺:pDNA complexes. This transfection system, comprised noncovalent assembly of cyclodextrin:adamantamethamidyl-modified hyaluronic acid via host:guest interactions to condense pDNA, is a potentially useful tool for targeted delivery of nucleic acid therapeutics

Organocatalytic Synthesis and Evaluation of Polycarbonate Pendant Polymer:β-Cyclodextrin-Based Nucleic Acid Delivery Vectors

A family of mPEG-<i>b</i>-polycarbonate (mPEG-PC) diblock pendant polymers were synthesized from trimethylene carbonate and other cyclic carbonate monomers bearing hydrophobic guest ligands via organocatalytic ring-opening polymerization using 1,4,5-triazabicyclo[4.4.0]­dec-5-ene catalyst or 1,8-diazabicyclo[5.4.0]­undec-7-ene/thiourea cocatalyst. Diblock copolymers composed of a methoxy­poly­(ethylene oxide) (mPEG) block and a polycarbonate block containing either homopolymer or mixed polycarbonates (PC) were prepared by homopolymerization or copolymerization of the cyclic carbonate monomers in the presence of mPEG2000 or mPEG5000 initiator to give materials having a tunable pendant group density along the polycarbonate backbone. Polycarbonate blocks targeting the 2.4–10 kDa range were prepared with good molecular weight control and modest polydispersities (averaging ∼1.3). Complexation of plasmid DNA with β-cyclodextrin–polyethylenimine2.5 kDa produced nanoparticle cores that were then coated with the mPEG–PC diblock copolymers to produce transfection complexes in the 100–250 nm size range. Stable transfection complexes prepared at N/P ratios >10 had slightly positive ζ potentials and showed comparable or modestly better transfection efficiencies in HeLa cells than the commercial transfection agent, Lipofectamine2000. Transfection efficiencies were not dependent on polycarbonate block molecular weights. The mPEG-PC constructs displayed similar efficacy for adamantyl and cholesteryl pendants that strongly bind to β-cyclodextrin; however, slightly better performance was observed for the weakly bound pendant, benzyl. These findings suggest that pDNA release is largely mediated by hydrolysis of the ester-bound pendant ligand within the endolysosomal compartment of the cell, with desorption of the mPEG–PC layer also contributing to plasmid release and activation in the case of weak binding pendant groups. We infer from these results that mPEG-PC may be an effective degradable transfection agent for <i>in vivo</i> applications