The delivery of drugs through the oral route is regarded as most optimal to achieve desired therapeutic effects and patient compliance. However, poor pharmacokinetic profiles of oral drug candidates remains an area of concern, and approaches to enhance their bioavailability are widely cited in the literature. Traditionally, the approaches have been confined to molecular optimization of the drug molecule, which has gradually evolved into development of microsized and nanosized formulations. Nanoformulations, by virtue of their nanosize, are widely acclaimed for circumventing the obstacles of poor pharmacokinetics. In this review, an attempt has been made to discuss existing challenges of bioavailability and approaches to overcome the same, with in-depth compilation of the literature on nanoformulations. The nanoformulations reviewed include nanocrystals, nanoemulsions, polymeric nanoparticles, self-nanoemulsifying drug delivery systems, dendrimers, carbon nanotubes, polymeric micelles and lipid nanocarriers. This review confirms the potential of nanomedicines to improve the pharmacokinetics of drugs via nanoformulations. Chemotherapeutic applications and patent reports are also compiled in the review. Despite the promising benefits, nanomedicines are associated with hazards to human health. Hence, the review also deals with toxicological consequences of nanomedicines, and with in vitro/in vivo screening methods to assess bioavailability as per regulatory considerations. Nanotechnology has been shown to facilitate the clinical translation of drug candidates that were deemed to be bioavailability failures. Conclusively, nanotechnological approaches to particle design and formulation are beginning to expand the market for many drugs with improved bioavailability and therapeutics. However, dedicated efforts are needed to develop advanced nanomedicines with minimal or no adverse effects.

Oral Bioavailability: Issues and Solutions via Nanoformulations

Considering the importance of drug permeation from formulations, in vitro and ex vivo drug permeation characteristics of three oral mucoadhesive suspensions of Ofloxacin were designed and compared. Three suspensions of Ofloxacin were prepared by taking two grades of Carbopol polymer such as Carbopol 934 (C934) and Carbopol 940 (C940); and Hydroxypropyl methylcellulose. The permeability study was performed by using a Franz diffusion cell through both synthetic cellulose acetate membrane and excised goat gastrointestinal membranes in acidic as well as alkaline pH. To know the permeability of the drug from control/formulations through different membranes in acidic/alkaline pH, cumulative percentage drug permeation, apparent permeability (Papp) and flux (J) were calculated. In addition, enhancement ratio (ER) of each formulation was also determined. From our results, it is evident that formulation containing C940 was the best suspension considering Papp and J values of all formulations. Moreover, it was the most beneficial formulation for improving permeation and diffusivity of Ofloxacin even after 16 h. Hence, this suspension was probably the most suitable formulation to obtain prolonged release action of the drug. The ER values of all formulations through the excised goat intestinal mucus membrane in alkaline pH were higher than those formulations through the goat stomach mucosal membrane in acidic pH. ER values of those formulations indicate that the permeability of the drug was more enhanced by the polymers in the intestinal part, leading to more bioavailability and prolonged action in that portion of the gastrointestinal tract. It may also be concluded from our results that in addition to formulation containing C940, other formulations may also show effective controlled release action.

Effect of different polymers on in vitro and ex vivo permeability of Ofloxacin from its mucoadhesive suspensions.

A new spiro[indole-3,3'-pyrrolizine] derivative is regioselectively synthesized by the straightforward multicomponent reaction of 1-(4-fluorophenyl)-3-phenylprop-2-en-1-one, isatin and L-proline without any catalyst. The structure of the newly synthesized compound is characterized by IR, NMR, UV-visible and mass spectral data. The compound is also screened for its reducing power assay.

https://www.mdpi.com/1422-8599/2013/2/M802/pdf

2'-[(4-Fluorophenyl)carbonyl]-1'-phenyl-1',2',5',6',7',7a'-hexahydrospiro[indole-3,3'-pyrrolizin]-2(1H)-one

The kinetics of oxidation of cyclanols, viz., cyclohexanol, cyclopentanol, cycloheptanol and cyclooctanol by quinaldinium fluorochromate has been studied in aqueous acid medium at 313 K (±0.1 K). The cyclanols were converted to the corresponding cyclic ketones. The order of reaction was found to be one with respect to oxidant and fractional with respect to the substrate and hydrogen ion concentrations. Increase in the percentage of acetic acid increases the rate of reaction. The reaction mixture shows the absence of any free radicals in the reaction, which has ruled out the possibility of a one-electron transfer during the addition of acrylonitrile. The reaction has been studied at four different temperatures and the activation parameters were calculated. From the observed kinetic results a suitable mechanism was proposed. The relative reactivity order was found to be cyclohexanol < cyclopentanol < cycloheptanol < cyclooctanol. This was explained on the basis of I-strain theory.

/pdf/reactivity-of-cyclanols-towards-quinaldinium-fluorochromate-59m11uhu55.pdf

Reactivity of Cyclanols Towards Quinaldinium Fluorochromate Oxidation.

Two-electron transfer complimentary reaction between Waugh type enneamolybdomanganate(IV) and allyl alcohol is investigated in perchloric acid medium. The reaction is first order with respect to both the reactant and the order with respect to H+ ion is 1.45. The activation parameters were also determined and a possible complimentary two electron transfer mechanism is suggested for the reaction between allyl alcohol and Waugh-Type Enneamolybdomanganate(IV)

/pdf/kinetics-and-mechanism-of-oxidation-of-allyl-alcohol-in-23jancza7e.pdf

Kinetics and Mechanism of Oxidation of Allyl Alcohol in Perchloric Acid Medium by Waugh-Type Enneamolybdomanganate(IV)

The Oxidation of m-toluidine by sodium dichromate has been studied both spectrophotometrically (640nm) and iodometrically in aqueous nitric acid medium. The reaction is said to follow consecutive reaction mechanism. The reaction shows substrate inhibition at low H+ concentration. Oxidation proceeds by two routes and both routes give the colored product. Suitable mechanism is proposed. The rate constants, equilibrium constants and kinetic parameters are calculated.

/pdf/kinetics-of-oxidation-of-m-toluidine-by-sodium-dichromate-gs49dwpgjr.pdf

Kinetics of oxidation of m-Toluidine by Sodium Dichromate

The Oxidation of m-Toluidine by Cr(VI) has been studied both spectro-photometrically (640 nm) and Iodometrically in aqueous nitric acid medium in presence of micelles (CPC, Cetyl Pyridinium Chloride; Tween-20, Polyoxyethylene Sorbitan Monolaurate) and is said to follow a consecutive reaction mechanism. Kinetic parameter can not be calculated from absorbance data because absorbance after showing maximum showed marginal dip indicating that the decomposition of colored product is slow. Reaction is retarded by both the surfactant. At high concentration of detergents, the Toluidine concentration had no effect on the reaction rate. Mechanism with the associated reaction kinetics is assigned and discussed.

Ritu Singh

Papers

Kinetics of oxidation of m-Toluidine by Sodium Dichromate

Kinetics of Micelle catalyzed Oxidation of m-Toluidine