Quantification of Venlafaxine in Tablet Dosage Form

Quantification of Venlafaxine in Tablet Dosage Form New chiral normal phase UFLC method for determination of venlafaxine hydrochloride enantiomers in pharmaceutical formulations ABSTRACT Aim: A simple, specific, precise, sensitive and rapid normal phase-UFLC method was developed for determination of venlafaxine hydrochloride enantiomers in pharmaceutical formulation. Methodology: The method was developed on a Lux amylase 2 column (150 x 4.0 mm I.D., particle size 5 ÃŽ ¼); the mobile phase was n-hexane and ethanol (97:3 v/v); in 0.1%diethyamine using UV detector was fixed at 254 nm with a flow rate was 1 mL/min. Results: The retention time (tR) of R- venlafaxine hydrochloride and S- venlafaxine hydrochloride were found to be 4.5 ±0.2 min and 5.3 ±0.3 min, respectively. The linearity over the concentration range of 5-30  µg mL-1 for venlafaxine. The intra-day and inter-day coefficient of variation of the assay method were found to be 0.293 to 1.760 and 0.319 to 0.210 respectively, with high accuracy and precision results. The proposed NP-UFLC method is suitable for analysis of venlafaxine hydrochloride enantiomers in pharmaceutical dosage forms. Conclusion: The validated NP-UFLC method was developed for the quantification of venlafaxine in tablet dosage form. Keywords: R-venlafaxine hydrochloride, S-venlafaxine hydrochloride, enantiomers, NP-UFLC, Validation INTRODUCTION Venlafaxine is a second-generation antidepressant drug marketed as a racemic mixture (Figure 1). The R-enantiomer exhibits dual presynaptic inhibition of serotonin and noradrenaline uptake, whereas the S-enantiomer is a serotonine reuptake inhibitor. Thus, the drug is the first and most commonly used serotonin and noradrenaline reuptake inhibitor. Its synthesis and that of several analogues were described many years ago. The synthetic routes are similar and vary according to the nature of the aromatic substituents. However, the final products are racemic mixtures, and they were crystallized as hydrochlorides.[1] Although the disposition of venlafaxine in humans was originally found not to be stereoselective.[2] In view of the near expiration date (June 2008) of the first patent for the racemic compound and of these recent clinical findings, venlafaxine appears to be a good candidate for a chiral switch.[3-4] Figure 1: Molecular structure of Venlafaxine The trend toward single enantiomer drugs is clear and the number of racemic drugs that reach the market as new chemical entities is decreasing.[5] The relevance of chirality in antidepressant drugs was highlighted several years ago and many examples are illustrated in a recent very complete review.[6-7] In the previously cited research on the resolution of venlafaxine, the enantiomers were separated by either of two general approaches. The first is the classical method of diastereoisomeric salt formation and fractional crystallization and the second approach uses analytical enantioselective electro driven methods. In the latter cases, either cyclodextrinsin capillary electrophoresis.[8] There is only one literature report where an HPLC baseline separation of the enantiomers of venlafaxine extracted was achieved using a CSP and normalphase mode.[9] From an analytical point of view, enantioselective chromatography offers the advantages of a method that can be developed on a semiprepara tive or preparative scale for the isolation of single enantiomers, which then become available for pharmaceutical testing strategies and requirements for enantioselective.[10] In the present research work, a simple, sensitive and accurate normal phase UFLC method to separate R and S-enantiomer of venlafaxine in bulk drugs and tablets using Lux amylase 2 column column has been reported for first time. The method was also validated to ensure the compliance in accordance with the ICH guidelines. MATERIALS AND METHODS Chemicals and Reagents: Venlafaxine hydrochloride enantiomers were a gift sample from R N FINE CHEMICALS BANGALURU, India. The solvents like n-hexane and ethanol diethylamine used was of HPLC grade (Merck, India). Commercially available racemic venlafaxine hydrochloride tablets claimed to contain 25mg of drug were procured from local market. Instrumentation: Quantitative NP-UFLC was performed on gradient high pressure liquid chromatography (Shimadzu) auto sampler consisting of a LC–20HT solvent module, SPD– 10A, and an PDA detector with LC software. The column used was LUX amylase 2 chiral column(150 x 4.0 mm ) particle size 5 ÃŽ ¼. UFLC conditions: The composition of the mobile phase was n-hexane and ethanol in the ratio of 97:03 v/v. They were filtered before use through a 0.2 mm membrane filter, degassed in a bath sonicator for 10 min. The mobile phase was pumped from the solvent reservoir to the column at a flow rate of 1mL/min, which yielded a column backpressure of 96 kg/cm2. The run time was set at 20 min and column temperature was ambient. The volume of injection loop was 20 mL. prior to injection of drug solutions, the column was equilibrated for at least 30 min with the mobile phase flowing through the system. The eluents were monitored at 254 nm and data was acquired, stored and analyzed with the LC 10 software. REAGENTS USED Mobile phase n-hexane and ethanol of HPLC grade was taken as mobile phase in the ratio of 97:3 % (v/v). Preparation of standard stock solution Standard stock solution (100  µg mL-1) of Venlafaxine hydrochloride was prepared by weighing exactly 10 mg of drug dissolved in isopropanol and diluted to 100 mL with same solvent. Preparation of calibration curve Aliquots of Venlafaxine hydrochloride ranging from 0.5-3 mL (each mL contains 100  µg mL-1) were pipetted into as a series of 10mL volumetric flasks. The volume was made up to the mark at with isopropanol. Aliquoets of 10 µL was injected (six time) into HPLC. The elution of the drug measured at 254.0 nm. The amount of venlafaxine hydrochloride present in the sample solution was computed from its calibration curve and it was constructed by plotting peak area of chromatogram against the concentration of Venlafaxine hydrochloride. The blank chromatogram and standard drug chromatogram were shown in figure 2 and 3 respectively. Linearity was 5.0-30  µg mL-1 for Venlafaxine hydrochloride was shown in figure 4. Figure 2: Blank chromatogram Figure 3: Standard Chromatogram of venlafaxine enantiomer Figure 4: Calibration curve of venlafaxine hydrochloride ANALYSIS OF TABLET DOSAGE FORM Five tablets (EFFEROX), each containing 25 mg of venlafaxine hydrochloride were weighed and finely powdered. Powder equivalent to 125 mg of venlafaxine hydrochloride was weighed and transferred to a standard volumetric flask. The contents were mixed thoroughly and filtered through a 0.45 ÃŽ ¼m membrane filter. 10 ÃŽ ¼L of the sample was injected in to UFLC system for the analysis. The peak profile and peak purity of both enantiomers are shown in Fig. 5, 6, 7 and 8. Figure 5: Peak Profile Enantiomer 1 Figure 6: Peak Profile Enantiomer 2 Figure 7: Peak Purity Enantiomer 1 Figure 8: Peak Purity Enantiomer 2 RESULTS AND DISCUSSION Validation of the method The developed method for the assay of venlafaxine has been validated as per the current ICH Q2 (R1) guidelines.[11] Analytical parameters The development of NP-UFLC method for the determination of enantiomers has received a considerable attention in recent past because of its importance in the quality control of drugs and drug products. The assay of venlafaxine hydrochloride enantiomers was resolved with good accuracy. The retention time (tR) of R- venlafaxine hydrochloride and S- venlafaxine hydrochloride were found to be 4.5 ±0.2 min and 5.3 ±0.3 min, respectively. A typical chromatogram of R-Venlafaxine hydrochloride and S- venlafaxine hydrochloride is shown in Figure 3. Tailing factor for both R-venlafaxine hydrochloride and S-venlafaxine hydrochloride was found to be 1.1 and 0.8 respectively. The calibration curve was constructed by plotting the peak areas against the concentration of R-and S-venlafaxine hydrochloride in 5-30  µg mL-1 were shown in the Figure 4. It was found to be linear with a correlation coefficient of 0.9971 for R-venlafaxine hydrochloride and 0.9992 for S-venlafaxine hydrochloride, the r epresentative linear regression equation being y = 10507X +2467.1 and y = 10654X +2065.8 for both the enantiomers respectively. The slope, y-intercept, and their standard deviations evaluated are presented in Table 1. Table 1: Regression and sensitivity parameters of enantiomer-1 and enantiomer-2 Accuracy and precision The amount of venlafaxine hydrochloride enantiomers in the matrix was calculated using following formula. % Recovery = T-A /SÃâ€"100 T–total amount of drug estimated, A-initial amount of drug in the tablet powder and S- amount of pure drug added. The results revealed (Table 2), high recovery of Venlafaxine hydrochloride enantiomers, indicating that the proposed method for the determination of venlafaxine hydrochloride enantiomers in the tablet is highly accurate. The intraday and inter day percentage relative standard deviation values were shown in Table 3. These values were within the standard limits. Table 2: Accuracy data of enantiomer-1 and enantiomer-2 Mean value of six determinations Table 3: Precision data of enantiomer-1 and enantiomer-2 Limit of detection and limit of quantification Limit of detection can be calculated using the following equation according to ICH guidelines: LOD = 3.3 x N/S LOQ = 10 x N/S where N is the standard deviation of peak areas of the drug and S is the slope of the corresponding calibration curve. The results are shown in Table 1. Assay of the drug The chiral NP-HPLC method developed in the present investigation was used to quantify venlafaxine hydrochloride enantiomers in tablet dosage forms. The obtained results are given in Tables 4. The average drug content was found to be 10.047 mg for R-venlafaxine hydrochloride and 9.978 mg for S-venlafaxine hydrochloride of the labelled amount in 25mg of racemic venlafaxine hydrochloride, respectively. Table 4: Assay of Venlafaxine Robustness of the method and stability of the solution The robustness of an analytical procedure has been defined by the ICH as a â€Å"measure of its capacity to remain unaffected by small, but deliberate variations in method parameters. The most important aspect of robustness is to develop methods that develop methods that allow for expected variations in method parameters. According to ICH guidelines, robustness should be considered early in the development stage of a method. The typical variations studied under this parameter are flow rate, wavelength and mobile phase composition. The results are tabulated in Table 5. Table 5: Robustness data of enantiomer-1 and enantiomer-2 CONCLUSION A simple, rapid and normal phase chiral UFLC method has been developed and validated for the enantiomeric separation of venlafaxine in tablet formulation. This method is precise, accurate, robust, and specific. Satisfactory results were obtained from the validation of the method. The short retention time (4.5 min for enantiomer 1 and 5.3 for enantiomer 2) obtained provides rapid determination of venlafaxine, which is significant for its routine analysis in quality control. The method exhibits an excellent performance in terms of sensitivity and robust. The experimental results of the present study showed that the proposed NP-UFLC method is simple, specific, precise, sensitive, rapid and accurate and is useful for separation of venlafaxine hydrochloride enantiomers in its pharmaceutical formulation. References Yardley JP, Husbands GE, Stack G, Butch J, Bicksler J, Moyer JA, Muth EA, Andree T, Fletcher H, James MNG, Sielecki AR 2-Phenyl- 2-(1-hydroxycycloalkyl)ethylamine derivatives: synthesis and antidepressant activity. J Med Chem 1990;33:2899–2905. Wang CP, Howell SR, Scatina J, Sisenwine SF, The disposition of venlafaxine enantiomers in dogs, rats and humans receiving venlafaxine. Chirality 1992;4:84–90. Ault A Big pharma is increasingly in getting a piece of the generic pie. The Scientist, 2005;19:36–38. Agranat I, Caner H, Caldwell J Putting chirality to work: the strategy of chiral switches. Nat Rev Drug Discov 2002;1:753–768. Arina V, Reeves JT, Senanayake CH, Song JJ, Asymmetric synthesis of active pharmaceutical ingredients. Chem Rev 2006;106 : 2734–2793. Ruffolo RR Chirality in ÃŽ ± and ÃŽ ²-adrenoceptor agonists and antagonists. Tetrahedron 1991;47:9953–9980. Hutt AJ. Drug chirality and its pharmacological consequences. In Smith HJ, editor. Introduction to the principles of drug design and action, 4th ed. Boca Raton: CRC Press; 2006. Pg no: 117–183. Fanali S, Cotichini V, Porra` R Analysis of venlafaxine by capillary zone electrophoresis. J Capillary Electrophor 1997;4:21–26. Caccamese S, Biance S, Carter GT, Direct high performance liquid chromatography separation and 11 analogues using amylose derivated stationary phase, Chirality 2009; 21: 569-577. Anderson S. Preparative chiral chromatography. A powerful and efficient tool in drug discovery. In: Subramanian G, editor. Chiral separation techniques, 3rd ed. Weinheim: Wiley-VCH; 2007. Pgno: 585–600. 1

Decrease Of Teen Pregnancy Rate :: essays research papers

The overall teen birth rate has declined by 16 percent from 1991 to 1997. â€Å"All states are recording a decline and it is the sixth year in a row that the teen birth rate has declined,† stated Donna Shalala, HHS secretary of U. S. Newswire. Although the birthrate among teens is decreasing and the percentage of teenagers who have had sexual intercourse is declining, it is a multi-fauceted problem affecting today’s youth. The government is taking in to consideration all possibilities and conditions with teen births to make an affective way to prevent it.   Ã‚  Ã‚  Ã‚  Ã‚  Teenage pregnancy is a condition that can be controlled in many instances. Congress’ campaign is â€Å"To reduce the teenage pregnancy by supporting values and stimulating actions that are consistent with a pregnancy-free adolescence,† stated the Speaker pro tempore Mr. Taylor of North Carolina. Congress’ goal is to balance the budget and reduce spending in the area of Medicaid funds, food stamps, and AFDC funds that are especially hard-hit by the teenage pregnancy problem. Reducing teenage childbearing through this campaign is likely to require more than eliminating or manipulating welfare programs.   Ã‚  Ã‚  Ã‚  Ã‚  A form of prevention funded by the Department of Public Health in Massachusetts is The Challenge Fund. It is a community-based approach to teen pregnancy prevention. These coalitions unite youth, family, and community in order to create and increase opportunities for youth development and leadership. It also increases awareness of ownership of the risks, costs and problems of teen pregnancy.   Ã‚  Ã‚  Ã‚  Ã‚  The Federal Government has invested millions of dollars into an abstinence education program for young adults that provide ways for them to avoid sexual activity at such a young age. The program teaches teens the importance of sustaining from sexual activity before marriage and the importance of a monogamous relationship in a marriage. It also teaches them the harmful effects psychologically and physically, of sexual activity at a young age.   Ã‚  Ã‚  Ã‚  Ã‚  Studies show a trend toward sexual abstinence and improved use of condoms as possible reasons for sudden change in the pregnancy rate decreasing. Other studies also show that teen abortions are steadily declining as well, ruling out abortion as a factor in the falling national teen birth rate. â€Å"The government cannot calculate an overall teen pregnancy rate, which includes live births and abortions, because ten states keep no figures on abortions,† stated Stephanie Ventura, a statistician with CDC’s National Center for Health Statistics.

Introduction To Ethics Essay

Ethics is the study of the nature of moral virtues and evaluates human actions. Ethics come from agreements between people, duty considerations and considerations of the consequences of various actions we involve ourselves into. Philosophical ethics is the study of morality through rational means guided in human well-being. The three subsections of philosophical ethics are; normative ethics-is the study of moral standards that makes us judge our actions as wring or wrong or good from bad. Meta-ethics – is concerned with the meaning of ethical judgments that is responsible for the truth and validity of our actions. Meta-ethics assists us determine whether an opinion can be applied to any situation at present or in future. It asks questions such as; what’s the meaning of ethical terms such as good and right, the motives for acting ethically, the nature of moral reason. Applied Ethics – is the application of moral philosophy to real-life situations that have been investigated in normative ethics and judged on the lessons of meta-ethics. According to Paul Newall article moral philosophy is divided into branches; meta-ethics and normative ethics. The two have some differences according to how they are applied in the day to day real–life situations. Normative ethics is concerned with ethical questions that guide us in all what we do on a daily such as â€Å"What has value? † and â€Å"What are our moral obligations? † such questions give us our character and personality. Meta-ethics on its side is concerned with philosophical questions about ethics such as â€Å"What is value? † and â€Å"What can make it the case that we ought to do something? †. A personal ethical situation I experienced involved my neighbor who was caught stealing neighbor at the market place. Since police officers were not around to arrest him the mob took the chance to bit and stone him in protest. Being a person I had known over a period of time, I felt ethically right to save his live from the swelling mob. At first, I had to stop the mob from biting and stoning him, through dialogue. But my greatest fear was that the mob may turn and direct their anger towards me because I was protecting to protect a criminal who has been terrorizing them, but this did not happen since the crowd listened and accepted my request. In my opinion, it was ethically wrong for my neighbor to steal what others had ethically through struggle and hard work. He thus deserved to be punished, but the way the mob chose to punish the offender was totally unethical since the federal laws and regulations that govern the state should be followed in such a case. Being a quite tricky situation, I requested the mob first to stop any further biting and stoning and took the chance to dialogue and discuss with them other possible ways of punishing the offender such as taking him to the law officers. The mob seemed not to reason ethically at first because the police had in many cases fallen short of providing adequate security and the residents had no trust in them anymore. When I finally won them, I narrowed further to the issue of acting contrary to the state laws and the implications of their actions and even explained to them that the offender has right to live. The reason for this approach was that the mob seemed to have no moral standards and obligations to judge between good and bad. In many occasion, the mob makes wrong decisions but evaluates their action after an ffence has been committed, in this case the death of my neighbor. In my opinion their action was bad and could not be justified ethically, philosophically the mob morality was not rational and was not grounded in the notion of human happiness for both the accused ad the accusers. According to Newall’s explanation of normative ethics, several ethical questions must be questioned by all the participants in the whole process. First, my neighbor should have analyzed whether his decision to steal had any moral obligation and any value. Such a personal question should have stopped him from making the decision to steal. His morals could have been provoked and changed of mind taking a decision to engage in a more productive activity rather than stealing. The mob as well should have questioned their morals before choosing their action. By stoning to kill it implies that their morals were all wrong because it is moral wrong to hurt anyone. The law is very clear and precise on what should be done in such a case, but because they never followed the law; their moral values are as well questionable. My action was guided by the value of life and that no one is supposed to take the law into their own hands by causing bodily harm to anybody. My moral obligation was to safe my neighbor because if I watched him stoned to death, my moral conscience and quit would haunt me because I should have acted to save him. In conclusion, all our actions and decisions should be guided by our morals values and that normative ethics must always prevail in any action. We are supposed to fully evaluate our actions and be ready to face the consequences of our actions.

The Odyssey, The Presence Of Divine Intervention Essay

Throughout the Odyssey, the presence of divine intervention overwhelmingly shapes the story as a whole. The relationship between humans and gods within the book can be characterized as one that provides humans options, commonly in the form of an omen and according to their choices, will result in a set punishment or appraisal. From an individual’s choices in life and the aforementioned trials, a god or goddess will positively or negatively impact the person’s life. This divine intervention drives people to practice holy acts out of self-interest and fear which reveals that all humans at their base are not altruistic but, selfish and only care for events that will promote their lives. Their faith in or fear of the gods also provide insight on humans’ tendencies to divert blame, and be scared of the unknown. Throughout the Odyssey each and every character serves as a median to demonstrate how the gods intervene in humans’ lives that they either favor or desp ise and according to their subjective views on these people, they will construct their fate. In various encounters throughout the book, Athena, the goddess of wisdom influences the lives of Odysseus’s family in order to improve their fate due to her favoritism for the persistent mariner attempting to return home and respect of his cleverness. 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