The field of medicine and pharmacy has over the recent past experienced tremendous growth with technological improvements making pharmacy and the analysis of drugs and characteristics of drugs much simpler. Drug analysis is a fundamental aspect of drug development. It is not confined to making improvements to drug but also assessing quality to ascertain their fitness for human consumption. Drugs are chemical compounds that are affected by a number of factors including temperature, moisture and contaminants among others. For this reason, technology has provided an analytical tool for analyzing the drugs.
Following the introduction of spectroscopy about half a century ago, the technology has found enormous use in the field of medicine and pharmaceuticals. Day in day out the world has been experiencing technological improvements and the pharmaceutical industry has not been spared by this wave. Earlier technologies and techniques majorly depended on chemical analysis that did not give adequate information pertaining to internal components of compounds such as drugs.
Pharmaceutical industry largely relies on the accuracy and precision of various analytical instruments used in analysis in order to acquire valid data. The precision and consequently the validity of any pharmaceutical drug is a critical aspect as it has the capacity to influence life and health. As such, drug testing, manufacturing and quality control procedures should be guided by strict, reliable and accurate procedures. This implies that analytical instrument in pharmacy should be reliable and accurate (Kar 12).
Technology has made the study of both organic and inorganic compounds extremely unproblematic. Fourier Transform Spectroscopy in particular has brought a sigh of relief to the pharmaceutical sector as it has made drug analysis and analytical testing procedures effortless. “Fourier transform infrared spectroscopy”, originates from a mathematical process known as Fourier transform that is used in the conversion of raw data into real spectrum. As compared to older forms of this technology, FTIR is a revolutionary innovation due to its level of accuracy, expansive applications and deep penetration. Precedent technologies analyzed compounds over a much-contracted range of wavelengths. This left out a lot of information that otherwise would have been used by scientists in drug study and analyses to improve drugs .FTIR has rendered all older instruments such as the dispersive infrared spectrometers totally outmoded. This has been occasioned the already-proven efficiency exhibited by the FTIR. Unlike other analytical instruments, the FTIR analyses compounds over a broad range of wavelengths .FTIR works by producing infrared and measuring what amount of light is absorbed by a either a gas, liquid or solid (Kar 32). For this reason, FTIR gives insights on the internal structure and patterns of compounds. Overall, in pharmacy, FTIR has found multiples advantages in all areas that dispersive spectrometer was applied. Among the advantages of this instrument, include;
- high signal to noise ratio
- high accuracy levels
- very narrow error range
- a very high resolution
- Interference from light is highly reduced
For the above-mentioned advantages, FTIR has found a myriad of applications in pharmaceutical analysis in industrial and analytical testing procedures. FTIR has been able to use various analytical methods such a titration, gravimetric, chromatography, electrochemistry, molecular fingerprinting and drug resolution tests among others to boost the pharmaceutical sector in terms of quality control and for the purposes of analysis.
Analytical techniques also play a key role starting from drug development up to marketing and post marketing. They help in the understanding of the chemical and physical stability of the drug, the impact of the design and the selection of the dosage form, assessing drug molecule stability, impurities quantization and identification amongst others.
Analytical technology therefore finds very high application in the pharmaceutical industries and some the elements of analytical instrumentation technology that are applied in this field are discussed conclusively below:
Diagnostic medicine relies on a myriad observations and measurements to determine or evaluate the nature of diseases. Clinicians look for deviations from the normal functioning of body cells and in particular those that have both quantitative and qualitative characteristics which are relatable to known symptoms .In addition to physical symptoms, diseases have the ability to alter the concentration of body chemicals in tissues, cells and fluids. This form the basis of conducting clinical tests .Therefore, FTIR does not only probe the chemical composition of a sample but also the precise position. As such, this process is known as finger printing .FTIR spectroscopy is within a range that correspond s to the molecular vibration modes. This acts a guide to get a good understanding of the chemical origins of intricate patterns associated with biological specimens. Subsequently the spectrum of biological specimens gives a clear picture of the structural intricacy of individual components and their relative abundances. Images generated by the FTIR are used to determine target sites of a pathogen and consequently design a treatment that is target oriented. Images provided by this instrument also gives insights pertaining to the kind of treatment that a given cell or tissue should be accorded. As such, this guides the pharmaceutical sector in the study of pathogen behavior and modification of drugs (Kar 52).
Drug dissolution testing
Drug dissolution is a test that is widely used by pharmaceutical engineers to control product and in formulation of drug design. It is actually a test that measures the rate of drug release as a f unction of time. Fourier transform infrared (TFIR) has found a lot of analytical application in the drug dissolution testing for drugs with a very high concentration. However, for ordinary tablets, FIR cannot be used due to their high level of absorbability to water. Understanding the rate and mode of drug diffusion in to the system is a fundamental aspect of drug development. Frontiers have the capacity to monitor the rate of drug diffusion in to the system and thus providing clinicians a window for making probable improvements.
Thermal analysis techniques are deep-rooted in all research laboratories including pharmaceutical laboratories .FTIR has recently widened considerably the sensitivity and accuracy of thermal analysis techniques. Thermal analysis in drug analysis is useful in studying the behavior of poly-phasic structures in drugs and excipients. Since thermal changes and moisture occur during drug storage, thermal analysis is important in evaluating activity levels in drugs, stability levels and levels of toxins. Drugs are made of chemical compounds of which minimal changes in temperature may have significant impact in terms of composition. Temperature changes beyond within the stability boundaries may lead to instability of chemical compounds and that way triggering internal reactions between constituent chemical elements. This means that changes in temperature could lead to changes in composition that affects various drug properties such as in vitro penetration, dissolution and consequently their safety and efficiency in treating a disease. Therefore, thermal analysis is a fundamental drug analysis strategy (Ford and Timmins, 35). The movement of electrons hugely affects thermal and elastic properties of structures. FTIR is one of the fundamental instruments used in the study of electron emission patterns among compounds. Through crystallography and the study of compounds internal structures, it has been able to link temperature changes with electronic movements that have further contributed to the analysis of pharmaceutical products such as drugs.
On the other hand, coupled with gravimetric analysis, thermal analysis gives insights to pharmaceutical engineers on issues related to drug composition changes. Internal reactions in a drug that might be started by changes in temperatures lead to changes in mass of the drug. FTIR has assisted in the analysis of internal structure of drug. The study of behavior patterns of drug molecules could be the starting point towards analyzing a drug strategy (Ford and Timmins, 81).
The titrimetric method of analysis dates back to the mid-18th century. Gay Lussac came up with the volumetric method invention that subsequently led to the origin of the word titration. The titration methods being used in various industries have undergone massive transformation from the days of Gay Lussac and most of them have become modernized therefore enabling them to find application in a wide variety of industries including the pharmaceutical industry. For instance, there has been the spreading of the non-aqueous method of titrations, the expansion of the weak acids and bases titrimetric method applications, potentiometric end point detection amongst others. The latter has particularly helped to improve the precision of titration methods. In the pharmaceutical analysis, the use of titration methods is very conspicuous, For instance, in the past, titrimetric methods have generally been used in captopril, gabapentin and albendozol determination in commercial dosage forms. Another application of this basic analytical technology has been the determination of sparfloxacin particularly using one of the new forms of this method that is the non-aqueous titration method (Kar 68).
In addition to the application of titrimetric technology in drug estimation, the technology has also been utilized in the estimation of pharmaceuticals degradation products.
Thin Layer Chromatography
This is one of the oldest analytical techniques that have recently found massive application in the pharmaceuticals industries. The technique is very popular in the analysis of various inorganic and organic materials mainly because of the hue host of advantages that it holds over other techniques. Some of these advantages include sample distinction flexibility, minimal sample clean up, a relatively extensive choice of mobile phases, low cost and large sample loading capacity. One of the applications of this analytical technology in pharmaceutical analysis relates to its use in the screening of unknown materials that may be present in bulk drugs. The analytical technique gives a significantly high degree of assertion that every probable component of the drug has been separated from the others. This analytical technology’s high specificity has been extensively exploited for quantitative analytical purposes by use of spot elution and later trailed by spectrophotometric measurement. Thin layer chromatography analytical technique has been used in steroids, celecoxib, pioglitazone and noscapine determination. The technology also plays a significant role in the drug development early stages especially in situations where there is inadequate information regarding the degradation or the impurities products in drug substances. Consequently, a lot of pharmaceutical impurities have been determined or identified using the Thin Layer Chromatography technology.
High Performance Thin Layer Chromatography
High – performance liquid chromatography
This is an advanced liquid chromatography form that is used in separating in complex molecule mixtures encountered in biological and chemistry systems so as to get a greater insight into the individual molecules role. The use of HPLC in pharmaceutical analysis can be traced back to 1980 when it was first used in an assessment of bulk drug materials. It is a method that has very high specificity and precision. Research has established that it is in fact the most utilized form of chromatography.
In the pharmaceutical industry, the technique has helped to answer very many questions. It has been the choice method of analysis in many quality control and assurance stages in the pharmaceutical industry. In addition to the analysis of drugs, this technology has also been used to analyze pharmaceutical impurities and degradation products.
This is another great separation technique used for the detection of organic compounds (especially the volatile ones). It combines on-line detection and separation therefore allowing accurate quantitative analysis of complex mixtures even those present in trace amounts like parts per trillion. The technique plays a key role in pharmaceutical products analysis. For instance, gas chromatography technology is highly utilized in the creation of products of high molecular mass such as thermally unstable antibiotics and polypeptides. The technique’s main constraint lies in the drug substances non-volatility and as a result, derivatization becomes mandatory. In recent times, the technology has been utilized for assay of drugs for example isotretinion and cocaine. It has also been used in residual solvents determination in betamethasone valerate.
This falls under the spectroscopic methods that are based on the absorption of natural ultraviolet absorption as well as chemical reactions. Spectrophotometry involves quantitative measurement of the transmission or reflection material properties as a wavelength function; the method is highly precise and consumes very little labor. The use of this technique in pharmaceutical dosage form analysis has significantly increased recently. The method is for example used in corticosteroid drug formulations as well as cardiac glycoside determination.
Near Infrared Spectroscopy
This is an analytical procedure that is very rapid and that can analyze multicomponent in any class matrixes. The method has found great application in the pharmaceutical industry recently especially in regards to the testing of raw materials, process monitoring and quality control. The growing pharmaceutical interest in this technology has mainly emanated from its many advantages over other spectroscopic analytical methods that include easy sample preparation that do not need pretreatment. In combination with multivariate data analysis, the technique brings forth very many perceptions in the analysis of pharmaceuticals both quantitative and qualitative (Holzgrabe, Wawer and Diehl 34).
Nuclear Magnetic Resonance
This method is utilized in the screening of drug molecules. A variety of state of the art Nuclear Magnetic Resonance approaches have been adopted and have found extensive application in pharmaceutical analysis. In recent times, these applications have mainly revolved around drug composition characterization, determination of drug impurity, drugs quantitation in biological fluids and pharmaceutical formulations.
The method also plays a key role in drug design particularly in in the determination of chemical structure. It generates 3D images or image visualizations of the compound in solutions therefore allowing the molecule structures to be defined down to the atomic level. Consequently, this allows pharmaceutical researchers to understand the functioning of the molecule in the human body and therefore develop drugs accordingly (Holzgrabe, Wawer and Diehl 44).
Phosphorimetry and Fluorimetry
The pharmaceutical industries are constantly looking up for responsive analytical techniques by using micro samples. In regards to this, fluorescence and phosphoric spectrometry are actually two of the analytical techniques that serve this purpose with very high precision and specificity. They are used in drug quantitative analysis especially those on dosage forms (Holzgrabe, Wawer and Diehl 82).
Centrifugation is another analytical technique employed in the field of pharmaceutical analysis. Centrifugation works on the principle of increasing effective density (g’s). A centrifuge is equipment fitted with an electric motor putting an object in rotational motion around a fixed axis. The circular motion subjected to the object causes denser particles to settle at the bottom of the suspension while lighter objects tend to separate at the top along the radial direction. This implies that the separation of the various particles suspended in any particular media happens as selective gravity applies on them through rotation in a centrifuge. Effective gravity increases with an increase in the radius of the centrifuge arms or with a change in the rate of the square of the rotation.
Centrifugation has found valuable applications in the pharmaceutical world assisting in the accomplishment of otherwise difficult tasks. The application of the centrifuge to medical ends has been in existence since historic times. Its application in the separation of cream from milk made opened pharmacists on the potential it held for the separation of substances in the lab for medical purposes.
Blood plasma and serums are separated by the spinning of blood in blood tubes for a given amount of time. The separation of these blood components is important in the testing and preservation of the blood. Contaminants in the blood can only be determined by the separation of the serum from the other blood components. The serum is then screened for contaminants such as free floating red blood cells and cold agglutinins are identified and separated. Additionally, due to the high demand for blood products such as plasma, everyday in emergency rooms, front centrifugations as an indispensable process in the processing of these products in time and in the quantities required (Kar 80).
Urinalysis, the process where urine samples are examined for possible identifiers of disease in human beings, finds great use for centrifugation. The urine is subjected to a centrifuge and the resulting, separated components examined with a microscope.
Pharmaceutical companies also find great use for the centrifuge in separation of chemicals for their analysis and production. The components used in the production of the various drugs are found in various natural compositions and need be extracted from these states to constituent forms for the production of the required drugs. Centrifugation often finds an important application in these processes which makes an integral part of any pharmaceutical laboratory with which many of these successes would be impossible/ non-existent.
These methods rely on the potential, current or charge in an electrochemical cell, to serve as the analytical signal employed in the determination of the components of a compound/ solution. In electrochemical analysis, five factors come into play in the determination of the composition of a solution, 1. The electrode potential identifies the form of the analyte at the electrode’s surface. 2. Concentration of the analyte at the electrode surface is not necessarily its concentration in bulk solution. 3. The analyte might be involved in other reactions other than the red-ox reactions. 4. Current is used in the determination of the rate of oxidation or reduction reactions. 5. Current and potential are independent, and it’s impossible to control both at the same time.
Application of these electrochemical principles enables pharmacists to conduct research in the making and composition assessment of important drugs. An example of this application is the electrochemical analysis of psychotropic drugs. Psychotic drugs are drugs with the capability to pass the blood- brain barrier and as such are used in the medication of cases such as schizophrenia and depression (Kar 93). These drugs are composed of tricyclic rings and as such contain sulfur and nitrogen atoms which are at a predisposition to react with oxidants, platinum metals, thiocyanate or halide complexes of metals and some organic metals. These reactions are crucial in the analytic point of view of the drugs.
Some psychotropic drugs such as fluoxetine react with organic compounds such as chrome azural S. Many psychotropic drugs can also be reduced with ease on a mercury electrode. Properties such as these have been heavily exploited in the determination and development of psychotropic drugs. Electrochemical reaction of these drugs is determined using different electrochemical methods such as cyclic voltammetry and differential pulse voltammetry. The availability of such methods for manipulation of these drugs makes it easy for the development of new psychotropic drugs.
Microscopy is an important field in analytical processes and utilizes the use of microscopes for the examination on the contents of the various sample compositions. The use of microscopes aides the researcher view objects that cannot be observed by the unaided eye. The importance of microscopy in pharmaceutical analysis is pivotal. The minute nature of chemical components comprising a majority of substances under analysis makes it an indispensable art. An application of microscopy in pharmaceutical analysis is broad, as the following illustrations will hope to suffice (Kar 108).
Immunohistochemistry and Microscopy Techniques
This field deals with the study of the immune system’s response to infected tissue and the chemistry involved in the body’s reaction to various infections. This field of study focuses on the study of the workings of antigens and antibodies in relation to their reaction to certain infections. The technique applied by scientists mimics the body’s natural processes in an artificial setting allowing the scientists to identify the antibodies generated against specific tissue to fight the invading antigens. This study is crucial in the development of vaccines which employ these findings to create a mock antigen which triggers the production of antibodies which protect the body from invasion by infectious, real antigens.
Microscopy in Biotechnology
Biotechnology is the exploitation of biological agents, using scientific principle for the creation of new, useful products and services for the advancement of human welfare. The nature of biotechnology requires that it mainly has to deal with microorganisms and tissue collected from the subject organism at cellular level. The origin of useful pharmaceutical products such as penicillin is attributed to biotechnology where a microorganism is exploited for the production of the drug which proved revolutionary in modern medicine (Kar 78). The advancement of biotechnology, needless to say, is therefore highly dependent on the successful application of microscopy as the subjects under study are minute and incapable of observation under the naked eye.
As above seen in the above-mentioned illustrations, contribution of FTIR in the field of medicine is huge. Current technological advancements in the field of spectroscopy have offered a completely new approach to drug design and analysis. Drugs are a sensitive aspect of not only human health but for the sake of the entire universe. Were it not for the current technological advancements, most contemporary issues facing the pharmaceutical industry could pose a big challenge to humanity.
In spite of the many improvements and breakthroughs in the pharmaceutical arena, the persistent problem of counterfeit drugs is still evident. It is therefore critical for the relevant authorities to test and analyze the pharmaceuticals getting into the markets. This should be done randomly periodically to eliminate these counterfeits.
In such situations, analytical technology finds application in that it is used to identify malpractice in the manufacture, the sale and the distribution of pharmaceutical products.
It is very evident that modern drug discovery could not be realized without the use of the current advanced analytical instruments. The analytical instruments in particular FTIR have helped to revolutionalize the pharmaceutical industry which has consequently undergone massive growth to the point that there are thousands of such companies that produce millions of different drug and pharmaceutical brands in the world.
Ford, James L, and Peter Timmins. Pharmaceutical Thermal Analysis: Techniques and Applications. Chichester: E. Horwood, 1989. Print.
Holzgrabe, U, I Wawer, and B Diehl. Nmr Spectroscopy in Pharmaceutical Analysis. Oxford: Elsevier, 2008. Internet resource.
Kar, Ashutosh. Pharmaceutical Drug Analysis: Methodology, Theory, Instrumentation, Pharmaceutical Assays, Cognate Assays. New Delhi: New Age International, 2005. Print.