Poly(3-methylpyrrole): vibrational dynamics, phonon dispersion and heat capacity.

Normal modes of vibration and their dispersions in poly(3-methylpyrrole) (P3MPy) based on the Urey-Bradley force field are reported. It provides a detailed interpretation of previously reported I.R. spectra. Characteristic features of dispersion curves, such as regions of high density-of-states, repulsion, and character mixing of dispersive modes are discussed. Predictive values of heat capacity as a function of temperature are calculated from dispersion curves via density-of-states.

Phonon dispersion and heat capacity in polyfuran.

A study of the normal modes of vibration and their dispersion in polyfuran (Pfu) based on the Urey-Bradley force field is reported. It provides a detailed interpretation of IR and Raman spectra. Characteristic features of dispersion curves such as regions of high density-of-states, repulsion and character mixing of dispersive modes are discussed. Predictive values of heat capacity as a function of temperature are calculated.

Maximizing the native concentration and shelf life of protein: a multiobjective optimization to reduce aggregation.

A multiobjective optimization was performed to maximize native protein concentration and shelf life of ASD, using artificial neural network (ANN) and genetic algorithm (GA). Optimum pH, storage temperature, concentration of protein, and protein stabilizers (Glycerol, NaCl) were determined satisfying the twin objective: maximum relative area of the dimer peak (native state) after 48 h of storage, and maximum shelf life. The relative area of the dimer peak, obtained from size exclusion chromatography performed as per the central composite design (CCD), and shelf life (obtained as turbidity change) served as training targets for the ANN. The ANN was used to establish mathematical relationship between the inputs and targets (from CCD). GA was then used to optimize the above determinants of aggregation, maximizing the twin objectives of the network. An almost fourfold increase in shelf life (~196 h) was observed at the GA-predicted optimum (protein concentration: 6.49 mg/ml, storage temperature: 20.8 °C, Glycerol: 10.02%, NaCl: 51.65 mM and pH: 8.2). Since no aggregation was observed at the optimum till 48 h, all the protein was found at the dimer position with maximum relative area (64.49). Predictions of the finally adapted network also reveal that storage temperature and solvent glycerol concentration plays key role in deciding the degree of ASD aggregation. This multiobjective optimization strategy was also successfully applied in minimizing the batch culture period and determining optimum combination of medium components required for most economical production of actinomycin D.

Vibrational dynamics of poly(L-isoleucine).

Normal mode analysis and their dispersion for poly(L-isoleucine) are reported by using Urey Bradley force field and Fourier transform IR. The calculated frequencies are found to be in reasonably good agreement with the Fourier transform IRspectra. Experimental measurements reported by Wunderlich et al. also support the calculated specific heat variation of poly(L-isoleucine).

Molecular vibrations and normal modes in L-prolyl-glycyl-glycine using Wilson GF matrix method.

Collagen is one of the most important proteins containing mostly proline hydroxyproline and glycine. In collagen, approximately 33 percent of the amino acid residues are glycine and they occur at every third position, whereas remaining percentage is constituted by mainly proline or hydroxyproline and some part by alanine etc. having no definite positional placement in the chain. Thus, a study of conformation of proline and glycine containing dipeptides and tripeptides is important for understanding the conformation of collagen as a sequence of its constituent amino acids. In the present communication, we have studied spectral features of L-proline, L-prolyl-glycine (PG), L-prolyl-alanine (PA), L-glycylglycine (GG), Collagen and L-prolyl-glycyl-glycine (PGG). We have carried out detailed normal mode analysis of only PGG, because interpretation of spectra of other proline and glycine containing peptides can be treated as derivatives of this molecule. Urey-Bradley force field, which involves non-bonded interactions in the gem and cis configurations is used for calculation of normal modes. The "best-fit" set of constants are generated for PGG.

Role of molecular geometry, valence charge distribution and vibrational modes in bioactivity of cyclodiene insecticides.

Fourier transform infrared spectral measurement and complete normal mode calculations have been carried out for heptachlor and wedge modes have been identified. In addition, valence charge distributions have been obtained for aldrin, endrin, heptachlor, beta-endosulfan, cis-chlordane, trans-chlordane, photo-cis-chlordane and photo-trans-chlordane using CNDO/2 (complete neglect of differential overlap) molecular orbital calculations. A toxicity parameter has been defined as the product of the charge distribution and surface area of the corresponding active wedges, depending on the interacting structural features. The variation of this toxicity parameter is generally in order and in agreement with the reported measurements based on the corresponding order of observed LD50 values. Because of the structural features, the toxicity in these cases is a surface phenomenon rather than a volume effect as in the case of Gammexane, wherein the insecticide binds itself to membrane channels. Because the biological activity is a dynamic rather than a static phenomenon, it is expected that the normal modes involving the wedge atoms play an important role.

Phonon dispersion in polyinosinic acid.

A study of the normal modes of vibration and their dispersion in polyinosinic acid [poly (I)] along the helix axis based on Urey-Bradley force field is reported. It leads to a better interpretation of Raman and FTIR spectra. A comparison of dispersion curves of poly (I) with poly (G) has been made. Characteristic features of dispersion curves, such as regions of high density-of-states, repulsion and character mixing are discussed. Predictive value of heat capacity as a function of temperature is reported.

Stability of ethacrynate sodium after reconstitution in 0.9% sodium chloride injection and storage in polypropylene syringes for pediatric use.

The stability of ethacrynate sodium (1 mg/mL) in 0.9% sodium chloride injection has been studied at 25 deg C and 5 deg C in polypropylene syringes by using a stability-indicating high-performance liquid chromatography assay method. The concentrations of the drug were directly related to peak heights, and the percent relative standard deviation based on 5 injections was 1.6. Mannitol, which is added as an excipient in the injection, did not interfere with the assay procedure. Two products of decomposition separated from the intact drug. At 25 deg C, there was no loss in potency after 14 days of storage or at 5 deg C after 22 days of storage. the pH value (6.5) of the injection remained constant throughout the study period. The drug was not adsorbed onto the syringes and the physical appearance of the injection did not change.

Stability of acyclovir sodium after reconstitution in 0.9% sodium chloride inection and storage in polypropylene syringes for pediatric use.

The stability of acyclovir sodium (10 mg/mL) in 0.9% sodium chloride injection has been studied at 25 deg C and 5 deg C in polypropylene syringes by means of a stability-indicating high-performance liquid chromatography (HPLC) assay method. The concentrations of the drug were directly related to peak heights, and the percent relative standard deviation (RSD) based on 5 injections was 1.0. At 25 deg C, there was no loss in potency after 30 days of storage, and at 5 deg C, the drug had begun to precipitate within 5 days. Therefore, the stability could not be investigated. The pH values of the injections were between 10.4 and 10.7. The drug was not adsorbed onto the syringes, and the physical appearance of the injection did not change.

Chemical stability of methylprednisolone sodium succinate after reconstitution in 0.9% sodium chloride injection and storage in polypropylene syringes.

The chemical stability of methylprednisolone sodium succinate (10 mg/mL) in 0.9% sodium chloride injection has been studied at 25 deg C and 5 deg C in polypropylene syringes by means of a stability-indicating high-performance liquid chromatography assay method. The concentrations of the drug were directly related to the peak height, and the percent relative standard deviation based on five injections was 1.2. Benzyl alcohol, which is added as a preservative, did not interfere with the assay. Two products of decomposition separated from the intact drug. At 25 deg C, the loss of potency was less than 10% after 4 days of storage. At 5 deg C, the loss of potency was less than 5% when the injection was stored for 21 days. After 17 days of storage at 25 deg C, the pH value of the injection decreased from 7.2 to 6.5, and there was no change in the pH value when the injection was stored for 21 days at 5 deg C. The drug did not adsorb onto the syringes, and the physical appearance of the injection did not change.

Stability of piperacillin sodium after reconstitution in 0.9% sodium chloride injection and storage in polypropylene syringes for pediatric use.

A stability-indicating high-performance liquid chromatography (HPLC) assay method was used to study the stability of piperacillin sodium (40 mg/mL) in 0.9% sodium chloride injection at 25 deg C and 5 deg C in polypropylene syringes. The concentrations of the drug were directly related to peak heights, and the percent relative standard deviation (RSD) based on five injections was 0.8. Three products of decomposition separated from the intact drug. At 25 deg C, the loss in potency was less than 10% after 5 days of storage, and at 5 deg C, it was less than 2% when stored for 28 days. The pH value of the injection decreassed from 5.3 to 4.4 when stored for 28 days at 5 deg C. The drug was not adsorbed onto the syringes, and the physical appearance of the injection did not change.

Stability of oral liquid dosage forms of ethacrynic Acid.

The stability of ethacrynic acid (2.5 mg/mL) in oral liquid dosage forms was investigated. Tablets in 0.05 M phosphate buffer (available commercially) in water were used to prepare the dosage forms. The effects of mannitol and sugar on the stability of ethacrynic acid were negligible. There was no change in the physical appearance of the oral liquid dosage forms or pH values during the study. There was, however, a new peak in the chromatogram from the products(s) of decomposition. An oral liquid dosage form of ethacrynic acid containing 0.05 M phosphate buffer and 10% mannitol was stable for 24 days when stored at 5 deg C and for only 3 days when stored at 25 deg C.

Stability of an oral liquid dosage form of glycopyrrolate prepared from tablets.

A stability-indicating assay method has been developed to quantify glycopyrrolate in an oral liquid dosage form. The developed method is accurate and precise and has a percent relative standard deviation of 1.8 based on 5 injections. The deomposition product and the excipients present in the dosage form did not interfere with the assay procedure. An oral liquid dosage form (0.5 mg/mL in water) that was prepared using 1-mg commercially available tablets was stable for 25 days (loss in potency, 8.2%). During that time, the pH value of the dosage form decreased from 6.8 to 6.6.

Stability of pentobarbital sodium after reconstitution in 0.9% sodium chloride injection and repackaging in glass and polypropylene syringes.

The stability of pentobarbital sodium (10 mg/mL) in 0.9% sodium chloride injection and pentobarbital sodium (50 mg/mL) after repackaging in glass and polypropylene syringes has been studied at 25 deg C by means of a stability-indicating high-performance liquid chromatography assay method. The concentrations of the drug were directly related to peak heights, and the percent relative standard deviation based on 5 injections was 1.7. The pH value of the sample, which was prepared by diluting the injection (50 mg/mL) to 10 mg/mL with 0.9% sodium chloride injection, decreased from 9.2 to 8.2. At this pH, the free base began to crystallize out in less than 24 hours. After the undiluted commercial injection was repackaged in glass or polypropylene syringes, there was no significant loss of potency after 31 days of storage at 25 deg C. The pH value of the injection remained constant at 9.2.The pentobarbital sodium in injection appears to be very stable, because the loss in potency was only about 6.2% after it was boiled in water for 1.5 hours.

Stability of hydrocortisone sodium succinate after reconstitution in 0.9% sodium chloride injection and storage in polypropylene syringes for pediatric use.

The stabilty of hydrocortisone sodium succinate (10 mg/mL) in 0.9% sodium chloride injection has been studied at 25 deg C and 5 deg C in polypropylene syringes by means of a stabililty-indicating high-performance liquid chromatography assay method. The concentration of the drug was directly related to the peak height, and the percent relative standard deviation based on 5 injections was 1.2. Benzyl alcohol, which was added as a preservative, did not interfere with the assay procedure. Two products of decomposition separated from the intact drug. At 25 deg C, the loss in potency was less than 10% after 7 days of storage. At 5 deg C, it was less than 3% when stored for 21 days. The pH value of the injection decreased from 7.2 to 6.3 when stored at 25 deg C for 21 days and from 7.2 to 7.0 when stored at 5 deg C for 21 days. The drug did not adsorb onto the syringes, and the physical appearance of the injection did not change.

Stability of nafcillin sodium after reconstitution in 0.9% sodium chloride injeciton and storage in polypropylene syringes for pediatric use.

The stability of nafcillin sodium (10 mg/mL) in 0.9% sodium chloride injection has been studied at 25 deg C and 5 deg C in polypropylene syringes by means of a stablilty-indicating high-performance liquid chromatograph assay method. The concentrations of the drug were directly related to peak heights and the percent relative standard deviation based on 5 injections was 1.2. The sodium citrate (added as a buffering agent in the powder) did not interfere with the assay procedure. The product(s) of decomposition separated from the intact drug. At 25 deg C, the loss in potency was less than 2% after 7 days of storage, and at 5 deg C it was also less than 2% when stored for 44 days. The pH values of the injections were between 6.2 to 7.0 throughout this study, except after 14 days of storage at room temperature (potency, 82.3%; pH,5.3). The drug did not adsorb to the syringes, and the physical appearance of the injection did not change. Nafcillin sodium was considered stable for at least 7 days at 25 deg C and 44 days at 5 deg C.

Stability of levothyroxine sodium injection in polypropylene syringes.

A stability-indicating high-performance liquid chromatography assay method was used to study the stability of levothyroxine sodium injection (100 micrograms/mL) in 0.9% sodium chloride injection after being stored at 5 deg C in polypropylene syringes. The method developed is accurate and precise and has a percent relative standard deviation of 1.3 based on 5 readings. The concentrations of the drug were directly related to the peak heights. The drug in the injection did not adsorb onto the polypropylene syringes. After 7 days of storage at 5 deg C, the injection was clear, the pH value had not changed, and there was no loss in the potency of levothyroxine sodium. The manufacturer's recommendation that the injection be used immediately after reconstitution is very conservative.

Stability of alatrofloxacin mesylate in 5% dextrose injection and 0.45% sodium-chloride injecion.

A high-performance liquid chromatographic assay method for the quantitation of alatrofloxacin in intravenous (IV) admixtures has been developed. The method is accurate and precise, with a percent relative standard deviation of 1.2% based on five injections. The method is stability indicating since the product of decomposition, trovafloxacin, did not interfere with the assay procedure. The IV admixtures of alatrofloxacin (1.88 mg/mL) in 5% dextrose and 0.45% sodium-chloride injections were stable for at least nine days when stored at room themperature. The pH values of the admixtures did not change and they remained clear throughout this study.

Stability of an oral liquid dosage form of trovafloxacin mesylate and its quantitation in tablets using high-performance liquid chromatography.

A high-performance liquid chromatographic assay method for the quantitation of trovafloxacin in film-coated tablets and an oral liquid dosage form (10 mg/mL) prepared from tablets has been developed. The assay method is very simple, precise and accurate, with a percent relative standard deviation of 1.8 based on five injections. The recovery from the tablets and the oral liquid dosage form was very close to the label claims. The method is stablilty indicating, since the peak from a degraded sample (using sodium hydroxide) did not interfere with the assay procedure. Furthermore, a number of excipients present in the tablets and the oral liquid dosage form did not interfere with the developed method. The oral liquid dosage form gave uniform results and the drug was stable for at least 14 days when stored in an amber-colored glass bottle at 25 deg C(+/-1). The pH of the formulation did not change.

Effect of sulphur crosslinking on the stability and transition of triple helical DNA.

In continuation to our work on order-order and order-disorder transition in triple stranded DNA when it is bounded to netropsin, we report in this communication the stabilizing/destabilizing effect of disulphide linkage on the phase dynamics of the triplex using the amended Zimm-Bragg theory. It is observed that in contrast to the sequential triplex-->duplex -->single strand melting of the uncrosslinked triplex, crosslinking causes the triplex state to melt directly to the single stranded state, with no apparent intermediary of a duplex state. Since there is no overall difference in the enthalpy of crosslinked and uncrosslinked triplexes, the transition is entropy driven.