A Critique of Computer Simulation Software's Used in Pharmacokinetics and Pharmacodynamics Analysis.

BACKGROUND: In the pharmaceutical sectors, the computer plays a crucial role as a commander of all the theoretical aspects and provides a workbench to improve the overall quality of pharmaceutical research and development. The aim of this article is to provide a computational approach to the development of numerous technology of computer software in the field of clinical pharmacokinetics. The computational technique practised by clinical pharmacist and scientist with the applied knowledge and skills in dealing with clinical pharmacokinetics problems can be applied in routine clinical practices. METHODS: To solve the various complicated pharmacokinetic equations and modeling of pharmacokinetic processes, various software were used like Population pharmacokinetics, Individual pharmacokinetics, Absorption, Distribution, Metabolism, and Excretion (ADME) pharmacokinetics, in - silico pharmacokinetics like Window-Based Non-linear model fitting (WinNonlin), Statistical Analysis Software (SAS), Non-linear Mixed Effects Modelling (NONMEM), PK Solution etc. Results: Various software's which was described in this paper help in the development of experimental study designs, statistical treatment of data and various simulation studies, etc. A robust software solution should be easy to use and address the three main parts of the PK-PD workflow like data management, analysis, and reporting. PK-PD software's allow researchers to predict ADME properties of new drug entity. For the study of the pharmacokinetic, the best software is WINBUGS where there is no limitation of dimensional array and size of the problem. The best software to be used for individual pharmacokinetics is T.D.M.S in which, we can apply Bayesian and least square method for curve fitting and it can be used for both linear and non-linear pharmacokinetic data. CONCLUSION: Various software were discussed here. This software not only help in knowing the history of the software but also help in gaining more knowledge about pharmacokinetics and pharmacodynamics simulation. Different software such as population pharmacokinetic, individual pharmacokinetic and others discussed in this article will help in the reporting and analyzing of data. The important points to be considered while selecting the software is also discussed which will help in easy accessing of software.

Lipid-polymer hybrid nanoparticles: Development & statistical optimization of norfloxacin for topical drug delivery system.

Poly lactic acid is a biodegradable, biocompatible, and non-toxic polymer, widely used in many pharmaceutical preparations such as controlled release formulations, parenteral preparations, surgical treatment applications, and tissue engineering. In this study, we prepared lipid-polymer hybrid nanoparticles for topical and site targeting delivery of Norfloxacin by emulsification solvent evaporation method (ESE). The design of experiment (DOE) was done by using software to optimize the result, and then a surface plot was generated to compare with the practical results. The surface morphology, particle size, zeta potential and composition of the lipid-polymer hybrid nanoparticles were characterized by SEM, TEM, AFM, and FTIR. The thermal behavior of the lipid-polymer hybrid nanoparticles was characterized by DSC and TGA. The prepared lipid-polymer hybrid nanoparticles of Norfloxacin exhibited an average particle size from 178.6 ± 3.7 nm to 220.8 ± 2.3 nm, and showed very narrow distribution with polydispersity index ranging from 0.206 ± 0.36 to 0.383 ± 0.66. The surface charge on the lipid-polymer hybrid nanoparticles were confirmed by zeta potential, showed the value from +23.4 ± 1.5 mV to +41.5 ± 3.4 mV. An Antimicrobial study was done against Staphylococcus aureus and Pseudomonas aeruginosa, and the lipid-polymer hybrid nanoparticles showed potential activity against these two. Lipid-polymer hybrid nanoparticles of Norfloxacin showed the %cumulative drug release of 89.72% in 24 h. A stability study of the optimized formulation showed the suitable condition for the storage of lipid-polymer hybrid nanoparticles was at 4 ± 2 °C/60 ± 5% RH. These results illustrated high potential of lipid-polymer hybrid nanoparticles Norfloxacin for usage as a topical antibiotic drug carriers.

Effect of in vitro transcorneal approach of aceclofenac eye drops through excised goat, sheep, and buffalo corneas.

The current study involves the evaluation of factors that influence the transcorneal permeation of aqueous drops of aceclofenac ophthalmic formulation through freshly excised goat, sheep, and buffalo corneas. Aceclofenac formulation with different concentrations 0.1-0.5% (w/v) and with different pH and different preservatives, was taken into account. The amount of drug permeated from different formulations was estimated using an Franz diffusion cell. A linear increase in drug permeation was observed with increase in pH (5.5 to 7.4). The apparent permeability coefficient was found to be maximum 15.01 ± 0.45 on goat cornea and maximum transport of aceclofenac was observed at physiological pH of tears (i.e., 7). The results advocate that aceclofenac 0.5% (w/v) ophthalmic solution (pH 7.0) containing BAK (0.01%) provides maximum in vitro ocular permeability through goat, sheep, and buffalo corneas.

Novel approach of aceclofenac fast dissolving tablet.

Fast disintegrating tablets (FDTs) have received ever increasing demand during the last decade, and the field has become a hastily growing area in the pharmaceutical industry. Upon introduction into the mouth, these tablets dissolve or disintegrate in the mouth in the absence of additional water for easy administration of active pharmaceutical ingredients. Aceclofenac, an NSAID, has been recommended orally for the treatment of bone and connective tissue disorder and thus the formulation of the same resulted in development of several FDT technologies. The present aim is to formulate a tablet which disintegrate and dissolve rapidly and give its rapid onset of action: analgesic, antipyretic and anti-inflammatory action. Besides, the conventional tablets also show poor patient compliance an attempt had been made to formulate for FDT of aceclofenac by using various super disintegrants like sodium starch glycolate, croscarmellose sodium and crosspovidone (polyplasdone XL) and PEG 6000 followed by novel technique. The tablets were evaluated for friability, hardness, weight variation, disintegration time, wetting time, in vitro dissolution studies and drug content studies. It was concluded that the batch which was prepared by using combination of crosspovidone and sodium starch glycolate as a super disintegrant shows excellent disintegration time, enhance dissolution rate, taste masking and hence lead to improve efficacy and bioavailability of drug.

Lead induced alterations in hemoglobin content during gestation and lactation in Swiss albino mice.

Number of studies in animal models has shown changes in hemoglobin content after lead administration during gestation and lactation, still lead induced hematological changes are not well established. In the present study, hemoglobin content of normal and lead exposed pregnant and lactating Swiss mice were compared. Pregnant females were exposed to heavy metal lead orally on diet containing 4.5% lead nitrate and lead acetate trihydrate during gestation to 3rd week of lactation. Hemoglobin content and blood cell counts were examined on 15th day of gestation and on 1st, 11th and 21st day after birth. The results indicated that in lead intoxicated pregnant females, hemoglobin content decreased. From the results of above study it can be concluded that high levels of lead exposure during gestation and lactation can severely damage heme synthesis.

Chemopreventive effect of hydroethanolic extract of Euphorbia neriifolia leaves against DENA-induced renal carcinogenesis in mice.

The present study was conducted to investigate the chemopreventive effects of hydro-ethanolic extract of Euphorbia neriifolia (EN) on N-nitrosodiethylamine (DENA) induced renal cancer in male Swiss albino mice. Animals were pretreated with EN extract (150 and 400 mg/kg body weight; p.o) and butylated hydroxyanisole (BHA) as a standard (0.5% and 1% BHA p.o) both for two week prior to the administration of single dose of DENA (50 mg/kg body weight; p.o). Various in vivo antioxidant biochemical parameters like lipid peroxidation (LPO), superoxide dismutase (SOD), and catalase (CAT) were evaluated to determine the reno-protective and antioxidant activity of EN. DENA increased oxidative stress through increase in LPO and decrease in antioxidant enzymes (SOD, and CAT). The EN extract significantly restored the antioxidant enzyme level in the kidney and exhibited significant dose dependant protective effect against DENA induced nephrotoxicity, which can be mainly attributed to the antioxidant property of the extract. This study rationalized the ethno-medicinal use of EN for protection against renal cancer.