By Douglas Graham
An emerging technology for pharmaceutical sample composition analysis, laser-induced, breakdown spectroscopy (LIBS), enhances production with added efficiency and waste reduction. The technique applies a high-power, pulsed laser to the surface of a sample to be analyzed. The pulsed laser beam vaporizes a small amount of material and produces an ionized gas called plasma, which has an elemental mixture representative of the composition of the object. The light emitted by the plasma is analyzed with an optical spectrometer, providing information on the atomic makeup of the vaporized material.
“LIBS is a method for analyzing the composition of samples in multiple locations,” explains Dr. Fernando Muzzio, professor and director at the Engineering Research Center on Structured Organic Particulate Systems at Rutgers University, Piscataway, NJ. “When a laser is focused on a portion of a sample, its molecules are broken into a gas composed of individual atoms. Energy is released in the form of light. Its frequency indicates which atoms are present in the specimen, and the intensity associated with each frequency, the number of atoms you have. So, the process comes close to being simultaneously quantitative and qualitative.”
Deployed for several years in a variety of manufacturing venues, LIBS has only recently made its way to the pharma industry. Pharma users praise the technology, as the process instantaneously provides an assessment of sample content uniformity, a three-dimensional snapshot of element distribution, and API quantitative measurement — all without sample preparation.
The determination of content uniformity is LIBS job one. The molecular structure of a typical pharmaceutical is made up of hydrogen, carbon, nitrogen, oxygen, and, more often than not, some mystery element. The LIBS process concentrates on this unknown component, which is then subjected to qualitative and quantitative analyses to determine the extent to which it is distributed within the tablet. According to most estimates, all but 10% of solid dosage forms are partly composed of one or more sulfur, chlorine, magnesium, potassium, aromatic rings, fluoride phosphorous, and/or calcium atoms. Tablets represent approximately 70% of all the drugs currently offered to the pharma marketplace.
LIBS also determines the distribution and composition of minor ingredients such as lubricants and glidant, a material facilitating flow. An indication of lesser element inconsistency is a red flag in pharmaceutical processing, as it signals a problem with the mixing process. The LIBS process works equally well for blends.
AT THE SPEED OF LIGHT
The tremendous speed at which LIBS works is partly attributable to the fact that no sample preparation is required and that the process is both chemistry- and solvent-free. The technology is therefore less complicated to learn and use and correspondingly is more time-friendly than other methodologies. A LIBS laser will very rapidly ablate up to thirty spots on a tablet and communicate volumes of data relating to its composition. Examples of the types of intelligence gathered may include an assessment of material distribution within a tablet, an analysis of the same tablet’s coating thickness region by region, and a tablet-to-tablet coating consistency comparison. LIBS proceeds one tablet at a time, or in lots, the latter being the obvious choice if the goal is to more quickly turn the testing gears.
“The pharmaceutical industry uses several processes to establish content uniformity,” says Stéphane Mallette, VP of business development at Pharma Laser (www.pharmalaser.com), a manufacturer of LIBS instrumentation in Boucherville, Quebec. “Most processes yield excellent results. NIR [near-infrared], for example, is a highly sophisticated technology that calls for deep chemometric knowledge on the part of practitioners. There are many opportunities for NIR to work hand-in-hand with LIBS, as the latter methodology can do some jobs the former is not equipped to perform.”
Coating thickness, for example, is not a NIR aptitude. In fact, a good deal of the data easily captured by LIBS is tough to snare using other methods, many of them labor-intensive, complicated, and time-devouring. Pharma and LIBS make for a good marriage as drug makers need fast and easy access to information that will nip in the bud any issue that might otherwise surface down the road.
Other methodologies, such as NIR, are also difficult techniques to master. In the case of NIR, proficiency is not even possible without a good deal of formal training and months if not years of on-the-job experience. LIBS is an easy learn by comparison. Many labs get up and running on the process after just a single day of orientation.
Here again, it’s time that’s of the essence. Using LIBS, pharma companies expedite the perfection process of works in progress and carry them to market ahead of the competition.
THE BENEFITS TO A PHARMA LAB
To a pharma lab, LIBS’s strongest selling assets must surely be its dexterity and the velocity at which the technology completes any task assigned. In less than one minute, the LIBS process determines dosage; informs on content uniformity; indicates in three-dimensions the distribution of active pharmaceutical ingredients (APIs), excipients, lubricants, and disintegrants; and measures coating thickness uniformity. The technology has many other pharma-relevant virtues as well:
LIBS uncovers potential problems overlooked by other technologies. Money doomed to be lost is saved because the discovery of deficiencies midprocess has staved off the damage control cash hemorrhage that would have occurred later.
The technology can do jobs that can’t be done quickly, economically, or competently by other technologies. Augmenting methodologies already at work in the lab, LIBS will lift an organization’s standard of excellence via its ability to perform analyses not previously doable. Moreover, LIBS is both a robust and very sensitive technology with the ability to detect to the levels of high parts per billion (PPB) and low parts per million.
Holdups are identified at the speed of light. Time and money are saved. LIBS has also been the recipient of a favorable review from the federal government. Recently, U.S. FDA (in partnership with the National Research Counsel of Canada) validated a method for dosage determination of an API in tablets using LIBS technology. This is a big step for LIBS, as it signifies the FDA’s recognition of LIBS deployment in the routine analysis of solid dosage forms.
Quality control improves with LIBS. Batch release using conventional methods is a pricey process, requiring heavy payment in the way of human resource allocation, time, and analysis. With LIBS, qualitative measurement becomes instantly achievable, and cost-building factors are vetoed.
“LIBS is a cutting edge technology with tremendous implications for pharma,” Mallette comments. “It offers a lot of ROI to the industry. For instance, it streamlines processes, saves time, and trims costs. It should not, however, be viewed as a replacement for traditional methodologies any more than email should rightly be considered a substitute for the telephone. LIBS best serves the pharmaceutical industry as an augmentation to processes already in use in laboratories. It complements rather than nudges aside well-established methodologies, adding efficiency and improvement to operations overall.”