The Major Challenges Facing The Pharmaceutical Industry Biology Essay

One of the major challenges confronting the pharmaceutical industry today is happening new ways to raise effectivity, lessening costs at the same clip as still finally developing new therapies that enhance human wellness. To impart a manus reference these challenges the ingestion of analytical engineerings and high-throughput machine-controlled platforms has been employed ; in order to execute more experiments in a shorter clip frame with increased informations quality.

In recent old ages, important technological progresss have been made in particle chemical science public presentation, system optimisation, sensor design, and informations processing and control. When brought together, the single accomplishments in each subject have created a step-function betterment in chromatographic public presentation. Ultra public presentation liquid chromatography ( UPLC ) is a new class of analytical separation scientific discipline that retains the practicality and rules of HPLC, while increasing the overall fretted properties of velocity, sensitiveness and declaration.

ACQUITY Ultra Performance LCa„? Systems take advantage of technological paces made in particle chemical science public presentation, system optimisation, sensor design, and informations processing and control. When taken together, these accomplishments have created a step-function betterment in chromatographic public presentation. Defined as UPLCa„? , this new class of analytical separation scientific discipline retains the practicality and rules of HPLC while increasing the overall fretted properties of velocity, sensitiveness, and declaration.

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Fig. 1: UPLC Diagram

In this thesis the range has been to make improved high sensitive liquid chromatography methods for the quantification of majority drugs in order to accomplish the better public presentations of the different events in the analytical concatenation to cognize the pureness and check. The specific subjects studied in this thesis are described below.

The thesis comprises of 7 chapters as described below

Chapter-1: Introduction

The chapter describes the experimental processs adopted for analytical method development, method proof and its application to analysis of pharmaceutical drugs. A to the full logic, rational and systematic attack was followed for UPLC method development based on chromatographic rules ( Figure-2 ) . All the processs adopted were as per US FDA guidelines.

Fig. 2: Over position of systematic procedure in Analytial Development

Fig. 3: Over position method proof parametric quantities

Chapter-2: Literature Survey

Chapter-2 provides a brief description about the class, solubility, stableness and Quantification in majority drugs about the selected molecules for these thesis

1. 5-alpha reductase drug – Compound-A ( Finasteride ) ,

2. 5-alpha reductase drug – Compound-B ( Dutasteride ) ,

3. Anti migraine drug -Compound C ( Zolmitriptan )

Anti migraine drug -Compound D ( Rizatriptan benzoate )

Chapter-3: Finasteride

In this chapter the class of 5-alpha reductase inhibitors were considered for the research work. In this class Finasteride compound was considered for the development and proof Purity and Assay method. Chemically it is described as N- ( 1,1-dimethylethyl ) -3-oxo- ( 5I±,17I? ) -4-azaandrost-1-ene-17-carboxamide. The emperical expression is C23H36N2O2. Molecular weight is 372.55 ( Fig:4 ) . It is a specific inhibitor of steroid Type II 5I±-reductase, an intracellular enzyme that converts the androgen testosterone into 5I±-dihydrotestosterone ( DHT ) .

Benign prostate hyperplasia ( BPH ) is an androgen-dependent, nonmalignant growing of the periurethral prostate secretory organ that consequences in expansion of the prostate secretory organ and urinary obstructor. Prostate malignant neoplastic disease, the most common malignant neoplastic disease among work forces over 50years with increasing prevalence with age, is the taking cause of malignant neoplastic disease decease. Finasteride ( FIN ) ( CAS 98319-26-7 ) , a member of the 4-azasteroid household, is a powerful inhibitor of 5-alpha-reductase, this synthesizes androgendihydrotestosterone ( DHT ) through the decrease of testosterone.

Fig. 4: Chemical Structure of Finasteride

After reappraisal so many analytical diaries and literatures, we observed all the published analytical methods are holding higher runtime and nomadic stage holding different composing of dissolvers, gradient plan and high injection volume ( 20AµL ) , no RP-UPLC method for quantification of Finasteride and its related drosss in Pharmaceutical majority drugs were non published. Here we were present first clip stableness bespeaking RP-UPLC method for Quantification of Finasteride and its related drosss in API majority drugs with shorter runtime 16.0 min, low injection volume, low flow rate ( 0.22 ml/min ) and solvent use besides less when comparison to bing published methods. The freshly developed method was to the full validated as per ICH usher lines. This RP-UPLC method was successfully used for everyday analysis of API majority drugs every bit good as preparations in Pharmaceutical industries.

The one-dimensionality scope of Finasteride assay method was constructed utilizing standardization criterions ( viz. , 0.0025-0.15 mg/mL ) . The % truth of Finasteride observed was within 99.1 -100.7 at 50 % ,100 % and 150 % degree ; while the method preciseness % RSD at 100 % degree is 0.25. Recoveries of Finasteride drosss were estimated at 0.05, 0.10,0.15,0.20,0.25 and 0.30 mg/mL and the average recovery of Impurities was 101.3, 98.9,101,100.2,100 and 100.70 % , severally. Finasteride was subjected to emphasize under the debasement conditions i.e base and peroxide hydrolysis and staying stress conditions like Thermal, UV, Visible, acid and H2O hydrolysis is stable. This validated method was used everyday analysis of quantification of check and its related drosss in pharmaceutical majority drugs.

Chapter-4: Dutasteride

In this chapter the class of 5-alpha reductase inhibitors were considered for the research work. In this class Dutasteride compound was considered for the development and proof Purity and Assay. Chemically known as ( 5I± , 17I? ) -N- { 2,5 Bi ( trifluoromethyl ) phenyl } -3-oxo-4-azaandrost-l-ene-17-carboxamide ( Fig:5 ) , is a man-made 4-azasteroid compound with anti androgenic activity. Dutasteride is used to handle benign prostate hyperplasia in work forces holding an hypertrophied prostate secretory organ and in the intervention of male pattern phalacrosis. It belongs to a category of drugs called 5I±-reductase inhibitors, which competitively and specifically inhibits type 1 ( active in the greasy secretory organs of most parts of tegument and liver ) and type 2 ( chiefly active in the generative tissues like prostate, seminal cysts, epididymides, hair follicles and liver ) isoforms of 5I±-reductase, an intracellular enzyme that converts testosterone to 5I±-dihydrotestosterone. The lessening in dihydrotestosterone degrees may extenuate or forestall expansion of the prostate secretory organ. Dutasteride does non adhere to the human androgen receptor.

Fig. 5: Chemical Structure of Dutasteride

After reappraisal so many analytical diaries and literatures, we observed all the published analytical methods are holding higher runtimes and nomadic stage holding different composings of dissolvers, gradient plan and high injection volume ( 20AµL ) , no RP-UPLC methods for quantification of Dutasteride and its related drosss in Pharmaceutical majority drugs were non published. Here we were present first clip stableness bespeaking RP-UPLC method for Quantification of Dutasteride and its related drosss in API majority drugs with shorter runtime 10.0 min, low injection volume, low flow rate ( 0.4 ml/min ) and solvent use besides less when comparison to bing published methods. The freshly developed method was to the full validated as per ICH usher lines. This RP-UPLC method was successfully used for everyday analysis of API majority drugs every bit good as preparations in Pharmaceutical industries

The one-dimensionality scope of Dutasteride assay method was constructed utilizing standardization criterions ( viz. , 0.0025-0.15 mg/mL ) . The % truth of Dutasteride observed was within 99.1 -100.7 at 50 % , 100 % and 150 % degree ; while the method preciseness % RSD at 100 % degree is 0.25. Recoveries of dutasteride drosss were estimated at 0.05, 0.10,0.15,0.20,0.25 and 0.30 mg/mL and the average recovery of Impurities was 98.9, 96.1,97.4,94.7,94.5 and96.1 % , severally. Dutasteride was subjected to emphasize under the debasement conditions i.e acid and base hydrolysis and staying stress conditions like Thermal, UV, Visible, peroxide and H2O hydrolysis is stable.

This validated method was used for everyday analysis for quantification of check and its related drosss in pharmaceutical majority drugs and dose signifiers.

Chapter-5: Zolmitriptan

In this chapter the class of Anti migraine drug were considered for the research work. In this class Zolmitriptan compound was considered for the development and proof Purity and Assay method. Chemically it is described as ( S ) -aˆ‹4-aˆ‹ ( { 3-aˆ‹ [ 2-aˆ‹ ( dimethylamino ) aˆ‹ethyl ] -aˆ‹1H-aˆ‹indol-aˆ‹5-aˆ‹yl } aˆ‹methyl ) -aˆ‹1,3-aˆ‹oxazolidin-aˆ‹2-aˆ‹one. The empirical expression is C16H21N3O2. Molecular weight is 287.16 ( Fig-6 ) .

Zolmitriptan is a man-made tryptamine derived function and appears as a white pulverization that is readily soluble in H2O. It is a selective 5-hydroxytryptamine receptor agonist of the 1B and 1D sub types drug, used in the acute intervention of megrim onslaughts with or without aura and bunch concerns.

Fig. 6: Chemical Structure of Zolmitriptan

After reexamining of so many analytical diaries and literatures, we observed all the published analytical methods are holding higher runtimes and nomadic stage holding different composings of dissolvers, gradient plan and high injection volume ( 20AµL ) , no RP-UPLC methods for quantification of Zolmitriptan and its related drosss in Pharmaceutical majority drugs and preparations were non published. Here we were present first clip stableness bespeaking RP-UPLC method for Quantification of Zolmitriptan and its related drosss in API majority drugs with shorter runtime 10.0 min, low injection volume, low flow rate ( 0.3 ml/min ) and solvent use besides less when comparison to bing published methods. The freshly developed method was to the full validated as per ICH usher lines. This RP-UPLC method was successfully used for everyday analysis of API majority drugs every bit good as preparations in Pharmaceutical industries.

The one-dimensionality scope of Zolmitriptan assay method was constructed utilizing standardization criterions ( viz. , 0.05-0.15 mg/mL ) . The % truth of zolmitriptan observed was within 99.1 -100.7 at 50 % , 100 % and 150 % degree ; while the method preciseness % RSD at 100 % degree is 0.25. Recoveries of zolmitriptan drosss were estimated at 0.05, 0.10,0.15,0.20,0.25 and 0.30 mg/mL and the average recovery of Impurities was 99.07, 98.4, 99.9, 98.7, 100 and 98.9 % , severally. Zolmitriptan was subjected to emphasize under the debasement conditions i.e acid, base and peroxide hydrolysis and staying stress conditions like Thermal, UV, Visible and H2O hydrolysis is stable.

This validated method was used for everyday analysis for quantification of check and its related drosss in pharmaceutical majority drugs and dose signifiers.

Chapter-6: Rizatriptan benzoate

In this chapter the class of Anti migraine drug were considered for the research work. In this class Rizatriptanbenzoate compound was considered for the development and proof Purity and Assay method. Rizatriptan is a 5-HT1 agonist triptan drug for the intervention of megrim concerns. Chemically it is described as N, N-dimethyl-5- ( 1H-1,2,4-triazol-1-ylmethyl ) -1H-ndole-3-ethanamine monobenzoate. The empirical expression is C15H19N5.C7H6O2. Its molecular weight is 391.47 and its chemical construction shown in Fig.7

Fig. 7: Chemical Structure of Rizatriptan Benzoate

Significant figure of methods has been reported for the analysis of Rizatriptan in human plasma and serum by liquid chromatography and liquid chromatography/mass spectroscopy. Quantitative analysis of formulated drug merchandise by micro emulsion electro kinetic capillary chromatography ( MEEK ) was besides reported. There are several HPLC methods have been reported for the analysis of Rizatriptan and its possible procedure drosss with higher runtimes and injection volumes. The UPLC enables bettering the sensitiveness and selectivity with a significantly lower turnaround clip. Therefore, it was the demand of the award to develop a simple, specific, rapid, economic and sensitive and stableness bespeaking analytical method for the quantification in majority drugs.

Here we were present first clip stableness bespeaking RP-UPLC method for Quantification of Rizatriptan and its related drosss in API bulk drug with shorter runtime 13.0 min, low injection volume, low flow rate ( 0.3 ml/min ) and solvent use besides less when comparison to bing published methods. The freshly developed method was to the full validated as per ICH usher lines. This RP-UPLC method was successfully used for everyday analysis of API majority drugs every bit good as preparations in Pharmaceutical industries.

The one-dimensionality scope of Rizatriptan assay method was constructed utilizing standardization criterions ( viz. , 0.05-0.15 mg/mL ) . The % truth of rizatriptan observed was within 99.1 -100.7 at 50 % , 100 % and 150 % degree ; while the method preciseness % RSD at 100 % degree is 0.25. Recoveries of rizatriptan drosss were estimated at 0.05, 0.10,0.15,0.20,0.25 and 0.30 mg/mL and the average recovery of Impurities was 100.9, 102.2, 100.2, 105.7, 101 and 100.7 % , severally. Rizatriptan was subjected to emphasize under the debasement conditions i.e peroxide hydrolysis and staying stress conditions like Thermal, UV, Visible acid, base and H2O hydrolysis is stable.

This validated method was used for everyday analysis for quantification of check and its related drosss in pharmaceutical majority drugs and dose signifiers.

Chapter-7: Summary & A ; Conclusion

Chapter 7 describes the brief sum-up of the above classs of the drugs including analytical method development, method proof and its application to routine analysis survey followed by decision.

List of Publications

Y.KotiReddy, G.V. Subba Reddy, K.N. JayaVeera, Kishore Kumar Hotha. A Stability bespeaking UPLC Method for Finasteride and Its Related Impurities. American Journal of Analytical Chemistry, Vol.No.3 ( 11 ) , Year 2012, Pages ( pp ) 737-745.

Y.KotiReddy, G.V. Subba Reddy, K.N. Jaya Veera, Kishore Kumar Hotha.

UPLC Method For The Determination Of Rizatriptan Benzoate And Its Related Impurities. International Journal of Analytical and Bioanalytical Chemistry, Vol.No.2 ( 4 ) , Year 2012, Pages ( pp ) 228-234.

Y.KotiReddy, G.V. Subba Reddy, K.N. Jaya Veera. A New Stability bespeaking RP-UPLC Method for Related substances in Zolmitriptan. African Journal of Scientific Research, Vol.No.1 ( 1 ) , Year 2011, Pages ( pp ) 50-62.

Y.KotiReddy, G.V.Subba Reddy, K.N.JayaVeera, Kishore Kumar Hotha. A Stability bespeaking UPLC Method for Dutasteride and Its Related Impurities. American Journal of Pharmtech Research, Vol.No.2 ( 6 ) , Year 2012, Pages ( pp ) 702-715.