Development and Greenness Assessment of HPLC Method for Studying the Pharmacokinetics of Co-Administered Metformin and Papaya Extract

Foods with medical value have been proven to be beneficial, and they are extensively employed since they integrate two essential elements: food and medication. Accordingly, diabetic patients can benefit from papaya because the fruit is low in sugar and high in antioxidants. An RP-HPLC method was designed for studying the pharmacokinetics of metformin (MET) when concurrently administered with papaya extract. A mobile phase of 0.5 mM of KH2PO4 solution and methanol (65:35, v/v), pH = 5 ± 0.2 using aqueous phosphoric acid and NaOH, and guaifenesin (GUF) were used as an internal standard. To perform non-compartmental pharmacokinetic analysis, the Pharmacokinetic program (PK Solver) was used. The method’s greenness was analyzed using two tools: the Analytical GREEnness calculator and the RGB additive color model. Taking papaya with MET improved the rate of absorption substantially (time for reaching maximum concentration (Tmax) significantly decreased by 75% while maximum plasma concentration (Cmax) increased by 7.33%). The extent of absorption reduced by 22.90%. Furthermore, the amount of medication distributed increased (30.83 L for MET concurrently used with papaya extract versus 24.25 L for MET used alone) and the clearance rate rose by roughly 13.50%. The results of the greenness assessment indicated that the method is environmentally friendly. Taking papaya with MET changed the pharmacokinetics of the drug dramatically. Hence, this combination will be particularly effective in maintaining quick blood glucose control.

Pharmacokinetics and Bioequivalence of Two Formulations of Eldecalcitol Capsules in healthy Chinese volunteers under fasting and fed conditions and effects of food on pharmacokinetic profiles

Aims： The objective of this study was to evaluate the bioequivalence of two formulations of eldecalcitol (0.75 μg ) under fasting and fed conditions, and to explore the effect of food on the pharmacokinetic (PK) properties of eldecalcitol in healthy Chinese volunteers. Methods： A single-center, open-label, randomized, three-period, three-sequence, crossover study was performed in 27 healthy Chinese volunteers under fasting conditions. Meanwhile, a two-way crossover study was performed in 28 healthy volunteers under fed conditions. Blood samples were collected at scheduled time spots from 0 hour pre dose to 168 hours post dose following administration of 0.75 μg eldecalcitol. The PK parameters for bioequivalence evaluation calculated by non-compartment analysis include Cmax, AUC and AUC. Monitoring of adverse events throughout the study. Results： The 90% confidence intervals of the test/reference AUC ratio and C ratio were within the acceptance criteria. Under the fasting condition, T values were 3.987 h and 3.489 h in subjects after given the test and reference formulation respectively. While in the fed study, the Tmax were 9.006 h and 6.007 h respectively. Therefore, the Tmax was significantly increased (P < 0.05) under fed conditions. No severe adverse events occurred during the study and all adverse events were mild and transient. Conclusion: The generic product of eldecalcitol was bioequivalent to the reference product in terms of the rate and extent of absorption under both fasting and fed conditions. Food intake prolongs the oral absorption of eldecalcitol but does not significantly influence the system exposure.

BIOEQUIVALENCE EVALUATION OF ORALLY DISINTEGRATING STRIPS OF RIZATRIPTAN IN MALE VOLUNTEERS UNDER FASTING CONDITIONS

Objective: A randomized, open-label, balanced, two-treatment, two-period, two-sequence, single-dose, crossover bioequivalence study comparing Rizatriptan 10 mg Orally Disintegrating Strips (ODS, test) with that of established Oral Lyophilisate Rizatriptan 10 mg, Maxalt-MLT® (reference) was conducted in 24 healthy male volunteers under fasting conditions. A single oral dose of 10 mg Rizatriptan was administrated to each volunteer. Methods: Plasma concentrations of Rizatriptan were determined by a validated LC-MS/MS bioanalytical method. The plasma concentrations of Rizatriptan were considered for statistical analysis and for establishing bioequivalence. Pharmacokinetic analysis was done by using the non-compartmental method. Pharmacokinetic parameters Cmax, AUC0→t, AUC 0→∞, t1/2, Tmax, and Ke1 were estimated for each subject and each treatment. Results: Ninety percent confidence intervals (90% CI) calculated for the ratio of AUC0→t, AUC0→∞, and Cmax values for the test and reference formulations were 96.91-110.30%, 96.24-109.07%, and 90.37-113.56%, respectively for Rizatriptan. The 90% CIs of AUC0→t, AUC0→∞, and Cmax values were totally within 80-125%. Conclusion: Based on a statistical analysis of the results, both formulations of Rizatriptan 10 mg, were found to be bioequivalent in terms of rate and extent of absorption under fasting conditions.

In vitro and in vivo Evaluation of Ibuprofen Nanosuspensions for Enhanced Oral Bioavailability

Introduction: The objectives were to prepare, characterize and in vivo evaluate different ibuprofen (IBU) nanosuspensions prepared by ultra-homogenization, after oral administration to rabbits. Methods: The nanosuspensions produced by ultra-homogenization were tested and compared with a marketed IBU suspension for particle size, in vitro dissolution and in vivo absorption. Five groups of rabbits received orally 25 mg/kg of IBU nanosuspension, nanoparticles, unhomogenized suspension, marketed product and untreated suspension. A sixth group received 5 mg/kg IBU intravenously. Serial blood samples were obtained after IBU administration. Results: The formulated nanosuspensions showed significant decrease in particle size. Polyvinyl Pyrrolidone K30 (PP) was found to improve IBU aqueous solubility much better than the other tested polymers. Addition of Tween 80 (TW), in equal amount as PP (IBU: PP:TW, 1:2:2 w/w) resulted in much smaller particle size and better dissolution rate. The Cmax achieved were 14.8±1.64, 11.1±1.37, 9.01±0.761, 7.03±1.38 and 3.23±1.03 μg/ml and the tmax were 36±8.2, 39±8.2, 100±17.3, 112±15 and 105±17 min for the nanosuspension, nanoparticle, unhomogenized suspension, marketed IBU suspension and untreated IBU suspension in water, respectively. Bioavailability of the different formulations relative to the marketed suspension were the highest for nanosuspension> unhomogenized suspension> nanoparticles> untreated IBU suspension. Conclusion: IBU/PP/TW nanosuspensions showed enhanced in vitro dissolution as well as faster rate and higher extent of absorption as indicated from the higher Cmax, shorter tmax and larger AUC. The in vivo data supported the in vitro results. Nanosuspensions prepared by ultra-high-pressure-homogenization technique can be used as a good formulation strategy to enhance the rate and extent of absorption of poorly soluble drugs.

Alternativas farmacéuticas: ¿pueden ser intercambiables?

Pharmaceutical alternatives are products with the same active moiety, but different salt, ester or pharmaceutical form. Regulatory agencies have different criteria for this kind of drug. The European Medicines Agency (EMA) accepts the generic substitution using these alternatives, whereas the Food and Drug Administration (FDA) only authorizes generic substitution of pharmaceutical equivalents. The objective of this paper is to describe some relevant aspects that should be considered before deciding on making a generic substitution with pharmaceutical alternatives. It is important to note that a pharmaceutical alternative must show no significant difference in the rate and extent of absorption (bioequivalence) in a well-conducted in vivo study when compared with the reference formulation. Current Mexican regulations state that generic substitution is possible using pharmaceutical alternatives when bioequivalence is demonstrated in in vivo studies conducted under the NOM-177-SSA1-2013 criteria. In conclusion, generic substitution with pharmaceutical alternatives is possible if these products demonstrate in vivo bioequivalence when compared with the reference product.

Bioavailability Enhancement Techniques for Poorly Soluble Drugs: A Review

Bioavailability is defined as the rate and extent of absorption of unchanged drug from its dosage form. The oral bioavailability of drugs with poor solubility and reasonable permeability is limited by the drug dissolution step from drug products. Low aqueous solubility is the major problem encountered with formulation development of new drugs. The article briefly highlights traditional and novel techniques that are used for solubility enhancement of BCS Class II drugs are discussed in this article. The Traditional techniques include use of co-solvents, hydrotrophy, micronization, change in dielectric constant of solvent, amorphous forms, chemical modification of drug, use of surfactants etc. Novel technologies are size reduction technologies, lipid based delivery system, micellar technologies, solid dispersion and many more.

Effects of Food on Bioavailability of Analgesics; Resulting Dosage and Administration Recommendations

Objectives To evaluate currently approved analgesics, that is, opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), anticonvulsants, and serotonin and norepinephrine reuptake inhibitors (SNRIs) used as analgesics, for 1) differences in pharmacokinetic parameters under fed vs fasting conditions and 2) factors involved in dosage recommendations in relation to food. Design Systematic review. Results Food effect on the rate, extent of absorption, or shape of concentration–time profile can alter the onset of action, duration of action, or tolerability of a medication. Based on 79 analgesic products reviewed, food effect dosage recommendations depend on whether an analgesic will be dosed on a regular interval around-the-clock vs on an as-needed basis, the shape of concentration–time profile, steady-state concentrations, the type of meals used in the pharmacokinetic study, and drug administration with regard to food in clinical trials. Overall, most opioids do not have food restriction and are taken without regard to food, with the exception of OPANA products and XTAMPZA ER. For many NSAIDs, food does not affect absorption characteristics, with the exception of ZORVOLEX and CELEBREX. Although NSAIDs are commonly to be taken without regard to food, prescribers recommend administering them with food to reduce their propensity for gastrointestinal adverse events. A larger percentage of anticonvulsants and SNRIs used as analgesics are taken with food to improve their tolerability. Of all analgesic products, seven NSAIDs and six opioids lack food effect information, maybe due to their approval before Food and Drug Administration food effect guidance. Conclusions Overall, because food effects could alter the onset and/or duration of pain relief, analgesic medication should be used as per labeled recommendations for proper pain management.

Development of Lipomer Nanoparticles for the Enhancement of Drug Release, Anti-Microbial Activity and Bioavailability of Delafloxacin

Delafloxacin (DFL) is a novel potent and broad-spectrum fluoroquinolone group of antibiotics effective against both Gram-positive and negative aerobic and anaerobic bacteria. In this study, DFL-loaded stearic acid (lipid) chitosan (polymer) hybrid nanoparticles (L-P-NPs) have been developed by single-emulsion-solvent evaporation technique. The mean particle size and polydispersity index (PDI) of optimized DFL-loaded L-P-NPs (F1-F3) were measured in the range of 299–368 nm and 0.215–0.269, respectively. The drug encapsulation efficiency (EE%) and loading capacity (LC%) of DFL-loaded L-P-NPs (F1-F3) were measured in the range of 64.9–80.4% and 1.7–3.8%, respectively. A sustained release of DFL was observed from optimized DFL-loaded L-P-NPs (F3). Minimum inhibitory concentration (MIC) values of the DFL-loaded L-P-NPs (F3) appeared typically to be four-fold lower than those of delafloxacin in the case of Gram-positive strains and was 2-4-fold more potent than those of delafloxacin against Gram-negative strains. The pharmacokinetic study in rats confirmed that the bioavailability (both rate and extent of absorption) of DFL-loaded L-P-NPs was significantly higher (2.3-fold) than the delafloxacin normal suspension. These results concluded that the newly optimized DFL-loaded L-P-NPs were more potent against both Gram-positive and negative strains of bacteria and highly bioavailable in comparison to delafloxacin normal suspension.

Assessing the Perpetuity of Tribe Indebtedness: An Empirical Analysis

‘Indebtedness’ of the tribes increases their woe. They live in inaccessible terrain with inadequate infrastructure. Living on subsistence, majority of them depend on borrowings to finance their budget deficit. Being in debt tends to become perpetual with several drastic consequences like being subject to exploitation through bonded labour, losing of assets or transfer of ownership of land and other assets under several pre-text to non-tribal or private lenders, etc. This indebtedness itself has other adverse social impacts on the tribes like the low level of education, ill-health, employment status etc. which has a spiral relationship with indebtedness. This study seeks to identify the various facets of their indebtedness from close quarters, find the extent of absorption of institutional credit by these tribes and identify the gap in their likely absorption perpetuating their indebtedness. It is based on the analysis of primary data collected through structured schedules directly from the respondents. It has been analysed using relevant statistical and econometric tools. It finds the perpetual aspect of tribes' indebtedness due to various ingrained social, cultural and economic factors. It suggests ways to end this perpetuity and amalgamate them on the path of development.

The Labor Market: An Overview from an Islamic Perspective

The concept of employment has some aspects that are integrated in order to achieve the balance of the workforce, both aspects of demand and supply of labor. The labor market is considered as the location of meeting between the demand for labor from both the private and Government sectors and the supply of labor available. The meeting of demand and supply of manpower can exert influence on the determination of the level of wage labor. In other words, the labor market plays a role in assisting the Government in the process of making employment-related policies such as the determination of the level of wages. This study, by employing library research, demonstrated that the concept of labor as seen from the viewpoint of Islam will be able to reach the concept of labor. It is not limited to the extent of absorption of labor, but also related how the level of the workforce that is capable of being managed by the Government to be more productive. The policy of wage rate in Islam is not limited to referring to balance demand and supply of labor. It also reviews the needs of a worker based on the principle of fairness and honesty, and protects both interests in the worker and the employer. The essence of Islamic economy in review market power based on the view of Islam shows its potential in generating equitable economy society and realize prosperity.