Erik Jonas Pedersen

NMR characterisation and transdermal drug delivery potential of microemulsion systems

The purpose of this study was to investigate the influence of structure and composition of microemulsions (Labrasol/Plurol Isostearique/isostearylic isostearate/water) on their transdermal delivery potential of a lipophilic (lidocaine) and a hydrophilic model drug (prilocaine hydrochloride), and to compare the drug delivery potential of microemulsions to conventional vehicles. Self-diffusion coefficients determined by pulsed-gradient spin-echo NMR spectroscopy and T(1) relaxation times were used to characterise the microemulsions. Transdermal flux of lidocaine and prilocaine hydrochloride through rat skin was determined in vitro using Franz-type diffusion cells. The formulation constituents enabled a broad variety of microemulsion compositions, which ranged from water-continuous to oil-continuous aggregates over possible bicontinuous structures, with excellent solubility properties for both lipophilic and hydrophilic compounds. The microemulsions increased transdermal flux of lidocaine up to four times compared to a conventional oil-in-water emulsion, and that of prilocaine hydrochloride almost 10 times compared to a hydrogel. A correlation between self-diffusion of the drugs in the vehicles and transdermal flux was indicated. The increased transdermal drug delivery from microemulsion formulations was found to be due mainly to the increased solubility of drugs and appeared to be dependent on the drug mobility in the individual vehicle. The microemulsions did not perturb the skin barrier, indicating a low skin irritancy.

Proton magnetic resonance spectra at 220 MHz of amino acids, porcine and bovine insulin and the A and B chains of bovine insulin

Abstract Proton magnetic resonance (PMR) spectra of 21 commonly occurring amino acids dissolved in CF 3 COOH or CF 3 COOD were recorded and analyzed in terms of proton chemical shifts, relative to (CH 3 ) 4 Si (TMS) as internal standard, and proton spin-spin coupling constants. The results were used for an analysis of PMR spectra of insulin and the individual A and B chains (as S -sulfonates), all dissolved in CF 3 COOH or CF 3 COOD. In the unusually high magnetic field applied (ca. 50,000 oersteds) large chemical shifts are found. Resonances from specific protons in arginine, alanine, asparagine, glycine, histidine, lysine, phenylalanine, threonine, and tyrosine residues are observed separately in single recordings. The γ-CH 2 protons of glutamic acid and glutamine residues form one separate band at 2.70 ppm, the CH 3 protons of leucine, isoleucine, and valine form another separate band at 1.00 ppm. Only proton resonances from cysteine, proline, and serine residues give no easily accessible evidence of their presence but they contribute significantly to the intensity versus chemical shift integrals.

Microwave spectra of isotopic 1,3,4-thiadiazoles. Molecular structure of 1,3,4-thiadiazole

Abstract The microwave spectra of 2-D-, 2-13C-, and 3-15N-1,3,4-thiadiazole, C2H2N2S, were assigned and combined with earlier measurements to give a substitution structure of 1,3,4-thiadiazole. The molecule is planar with the following structural parameters: S,C=1.721A C,N=1.302A N,N=1.371A C,H=1.077A The result is compared with structures of other heterocyclic molecules.

Microwave spectra of [13C] and [15N] pyridine N-oxides and a preliminary ring structure

Abstract Pyridine N -oxide and the four ring substituted pyridine N -oxides were prepared. The microwave spectrum of the parent species was reinvestigated to high J -values ( J max = 40) and centrifugal distortion constants determined. The microwave spectra of the four isotopic species were investigated, and selected lines were measured and corrected for centrifugal distortion. A preliminary substitution structure of the ring is derived and compared to the ring structure in pyridine. Significant differences were found in the CNC part of the ring, whereas C(3)C(4)C(5) is almost unaffected by the N -oxide formation.

Hydrogen NMR spectra of pyridazine and pyrazole containing 15N

Abstract Preparation and 1H NMR spectra are described for [15N]pyridazine and [15N]-pyrazole. CNDO/2 and INDO calculations of spin-spin coupling constants are reported for pyridazine, pyrazole, pyridine, pyrrole, and thiazole. For 2JNH and 3JHH correlations between experimental and calculated data are established.

NMR studies of pyridine-N-oxide. Determination of spectroscopic constants from [15N]-, [4-2H], and the parent species

Abstract Pyridine- N -oxide, [ 15 N]pyridine- N -oxide, and [4- 2 ]pyridine- N -oxide have been investigated by NMR spectroscopy. 1 H, 2 H, and 13 C spectra have been obtained and analyzed, in terms of chemical shifts and spin-spin coupling constants. Relaxation times have been measured for 2 H and 13 C and have been used to determine the correlation time τ c under the assumption of isotropic molecular diffusion. On the basis of experimental data and observed linewidth variations the nitrogen quadrupole coupling constant has been evaluated. The experimental data are correlated with semiempirical calculations within the azine series.

Preparation and microwave spectra of [18O] pyridine N-oxide and deuterated pyridine N-oxides. Complete molecular structure of pyridine N-oxide

Abstract [18O] Pyridine N-oxide and the monodeuterated species have been prepared and their microwave spectra investigated for J-values up to 10. The complete rs structure is determined from these data combined with data from earlier measurements on the 13C- and the 13N-substituted species [1]. The Nue5f8O bond length obtained here is intermediate between the typical single and double bond lengths found in other gas phase molecular structures. The structure of the Cue5f8Nue5f8C part of pyridine N-oxide is found to be significantly different from the corresponding part of the pyridine structure.

Carnosol. Crystal structure, absolute configuration, and spectroscopic properties of a diterpene

The structure and absolute configuration of naturally occurring Carnosol have been investigated by X-ray analyses. Crystal data are: orthorhombic P21212;a=15.762(1),b=13.755(1),c=7.7747(7) Å,Z=4,V=1688.2 Å3, andR=0.031 (2569 reflections). The absolute configuration is established at a significance level better than 0.995 according to HamiltonsR-factor test and is in accordance with that predicted experimentally by chemically means. Correlation of the solid-state IR pattern of the regions sensitive to hydrogen bonding (CO and OH stretching bands) with the X-ray crystal structure is excellent and shows, that even weak inter- and intramolecular hydrogen bonds may be unambiguously identified by IR spectroscopy. The variable-temperature nuclear magnetic resonance studies (NMR) show that the twinning of the signals from the isopropyl methyl protons cannot be due to hindered rotation but can be ascribed magnetic nonequivalence induced by the chiral centers.

Proton magnetic resonance spectra of glucagon at 220 MHz

Abstract The 1 HMR spectra of the polypeptide glucagon (29 amino acid residues) dissolved in CF 3 COOH, and of deuterated glucagon dissolved in CF 3 COOD were recorded at 220 MHz. A total of 214 observable proteon resonances were assigned to 15 spectral bands I–XV. About 65 proton resonances were assigned to spectral lines of width 5–10 cps, or to narrow spectral regions. Good agreement with earlier obtained data for insulin and its A- and B-chain S -sulfonates was obtained. Spectral effects of the slow conversion of glucagon to heptatri-fluoroacetylated glucagon were found and utilized in the assignment of the spectrum of natural glucagon.

NMR studies of pyridazine-N-oxide. Determination of spectroscopic parameters from the [15N]- and parent species

Abstract Pyridazine- N -oxide and [ 15N pyridazine- N -oxide have been investigated by NMR spectroscopy. 1 H and 13 C spectra have been obtained and analyzed, in terms of chemical shifts and spin-spin coupling constants. Relaxation times have been measured for 13 C and have been used to determine the correlation time π c under the assumption of isotropic molecular diffusion. From 1 H, 15 N INDOR experiments the lineshape of N(2) is determined; analysis of the lineshape yields 1 J NN and T qN(1). On the basis of experimental data and observed linewidth variations, the N(1) nitrogen quadrupole coupling constant has been evaluated. The experimental data are correlated with semiempirical calculations within the azine series.