History of Pharmaceutical Compounding

It is impossible to say when the concept of mixing substances for health and healing began. But hunter/gatherer civilizations understood medicinal properties of minerals as well as the flora and fauna around them including mold, fungi, and bacteria.

Since the earliest humans brought their curiosity and maladies to Earth, pharmaceutical compounding was used for treating illness, staying healthy, preparing their dead as well as religious practices and personal grooming purposes. These primitive compounders used plants and animals to develop the first therapeutic oils.

Aelius Galenus or Claudius Galenus often anglicized as Galen or Galen of Pergamon (130-200 AD) was a Greek physician and philosopher and a legend in his own time. He had as many professional interests as he had versions of his names.

Countless philosophers, authors, poets, and other contemporaries praised his thoughts and publications on medical practices.

Interesting video about Galen and all his interests. Video has no narration, only overlays of text so no sound necessary.

Emperor Marcus Aurelius spoke of him personally touting his prowess and uniqueness as a doctor and theorist and trusted Galenus to treat his armies and officers during a great plague brought on during foreign wars in AD169.

Galenus was a teacher of Pharmacy and Medicine in Rome as well as a practitioner. His thoughts on when and how to treat patients, most notably, his teacher, philosopher Eudemus, met with public displays of contempt in Rome. When treating Eudemus for quartan fever after other physicians had given up on him, Eudemus warned him he risked assassination for his heretical views on medicine.

He contributed a great deal to the concepts of pathology and his published principles of compounding medicines heavily influenced the Western world for 1,500 years. And even today, his name is the root of the category title of pharmaceuticals compounded by mechanical means: galenicals. Many of his procedures and preparations continue to exist in some form today. Even very commonplace ideas are influenced by his studies such as he was the developer of cold cream. He also contributed greatly to detailed anatomy in spite of being forbidden to dissect human cadavers by the Roman government. So he relied on primates as he surmised their anatomy was simliar to humans. He also wrote a great deal about psychology and psycho-therapy. He was a prolific thinker and author in many philosophical and medical areas.

Galenus’ work was translated into Arabic in the 9th century and remains today a strong influence of Islamic medicine that is tied closely to the Islamic culture. Muslim pharmacists founded the first apothecary offering a storefront for acquiring medicines in Baghdad in 754. The world’s first drugstore was managed by Jabir Ibn Hayyan (721–815 AD), the founder of chemistry science.

The Alchemy movement in the earliest centuries AD were pioneered by those wishing to mutate base metals into more valuable noble metals such as gold or to perfect a youth elixir to defy aging.

In medieval times, the long-lived Alchemy movement led to philosophical shifts from a religious influence over compounding processes to scientific method to separate fact from folklore.

This shift led to a rapid development of identification many more plants with medically useful properties.

This turn of events was the birth of modern chemistry and of pharmacy.

Galenus continued to influence modern pharmacology in the Middle Ages. Galenus’ complete works were translated into Latin. They were edited and printed in Venice in 1550.

Scientist pharmacists began isolating active ingredients contained within crude drug concoctions. Compounding pharmacists used fractionation or recrystallization to separate the active ingredients, like morphine from opium, to improve the usefulness and effectiveness of treatments.

Modern pharmaceuticals was born as medications were isolated from their natural sources or crude drugs. An interesting example of how isolation of components became a standard process is coal tar, a by-product of bituminous (black) coal. It was used topically to treat skin itching, inflammation, and thickened skin from conditions such as eczema, psoriasis, and dandruff.

German chemists began to isolate the hundreds of different coal tar constituents ultimately developing synthetic dyes. One of these was the first sulfa drug that led to modern antibiotic therapy. It was also coal tar exploration that created phenolic compounds to sterilize surgical instruments and clean wounds made famous by Joseph Lister.

Compounding pharmacists combined intuition and scientific method to develop an ever-widening array of medical cures and treatments. Allantoin produced by fly larva was discovered to rejuvenate damaged skin. Quinine alkaloids that treat malaria were derived from the bark of the South American Cinchona tree. The list of medicines from compounding pharmacists experimenting and exploring are nearly a limitless list.

In the 19th century, compounding was exclusively done by trained specialized chemists. Compounding was required for most medications. Being called chemists prior to this time (and still in England), during this time, in the US, chemists began being called druggists or pharmacists.

Pharmacists manually compounding worked well on a small basis. But by the 1920s, the drug companies required economies of scale for common drugs.

During World War II, mass production of drugs like antibiotics, aspirin, and chemotherapy took off. Large-scale drug manufacturing eventually became commonplace and overtook compounding.

As pre-manufactured drugs gained traction, by 1950, only 25% of drugs were compounded decreasing to <5% by 1960 and 1% by 1970. As compounding waned, pre-manufactured drug products exploded.

The use of manufactured drugs resulted in drastic changes in the pharmacist’s dispensing job. Pharmacists primarily dispensed pre-manufactured capsules and tablets instead of creating them. And the ethical standards prevented pharmacists from directly intervening in patient care as they were prohibited from discussing the prescription contents with patients. Prescription labels at the time did not include the name of the product as the prevailing thought was that divulging the drug name on the label violated the physician-patient confidentiality.

Patient care-oriented pharmacists abhorred this new near-mindless dispensary model that often included retail activities such as selling non-pharmaceutical merchandise and preparing soda fountain treats. One pharmacist, Eugene White, revamped this model bringing today’s community pharmacies into view. After working at a typical retail-oriented pharmacy in the 1950s selling a wide variety of merchandise, he set up his own pharmacy in 1957 and by 1960 completely morphed the various parts of his community pharmacy coining the phrase “pharmaceutical center.” He removed the soda fountain, candy, stationary, toys, gifts, and other sundries. He hired a receptionist to greet patients and set up a patient counseling area. He created a record system to track the history of patients’ prescriptions. model was so impressive, in the 1960s, the drug giant, McKesson, designed and established professional pharmacies based on White’s vision. As PharmD degree programs prepared pharmacists to provide patient care services and ethics changed, the professional pharmacist with fewer soda fountain duties was born and meeting the medication needs of patients including identifying drug interactions became the norm.

• 1638: John Johnstone, a Scottish apothecary founded a settlement in what would become New Jersey.
• 1653: Gysbert van Imbroch, a Dutch surgeon, practiced medicine and sold drugs in a general store in what would become New York. This may have been the first “drugstore” on the continent.
• 1630: The city of Boston is founded and Governor John Winthrop and his son took a keen interest in preparing medicine. They hired trained British apothecary, Robert Cooke, to teach and assist them in working with herbs imported from Europe. The son also utilized minerals such as saltpeter, mercury, tartar, antimony, sulfur, and iron to prepared compounds. He became one of the first in North America to prepare pharmaceuticals.
• 1646: William Davis of Boston operated the first dispensary in British North America.
• 1646: Elizabeth Gooking Greenleaf was the first woman to practice apothecary during the colonial era. In 1727, she and her husband opened an apothecary shop in Boston.
• 1729: Irish immigrant, Christopher Marshall, opened an apothecary shop in Philadelphia. He ultimately manufactured pharmaceuticals supplying medicine to Revolutionary War troops and apprentice training for future druggists and chemists. His business grew to a large-scale chemical processor and served as a drug wholesaler (druggist) to physicians and large landholders.
• 1805: Christopher Marshall’s daughter, Elizabeth, became the first American woman
  apothecary.
• 1821: His son, Charles, became the first president of the Philadelphia College of Pharmacy.

Early pharmacists trained through apprenticeships. The first US pharmacy school, the Philadelphia College of Pharmacy, opened in 1821. Over the next 50 years, advanced pharmacy degrees became the preference over apprenticeships, ultimately becoming a requirement to be a pharmacist in 1932.

In 1820, the U.S. Pharmacopeia (USP) was established to protect patients from poor-quality medicines. USP sets standards for medicines and dietary supplements for all drug production including compounding pharmacy preparations.

Compounding pharmacies are seeing a revitalization as personalized medical care increases. The trends in use of natural compounds for health and healing as well as technological innovations such as cell and gene therapy that bring hyper-personalized medicine into reality. These trends are partially reversing the 20th century eradication of compounding pharmacists as more precise and bio-identical therapies are demanded by patients.

Approximately 60,000 community pharmacies in the US offer compounding services. And approximately 8,000 specialty compounding pharmacies are in the US. Hormonal therapies, cell/gene therapies, pain management segments, as well as an aging population are expected to drive this trend of more compounding pharmacies is expected to escalate over the next decade. It is estimated that 1-3% of the prescriptions issued in the US are for compounded drugs. (Statistics from biospace.com)

The challenges facing this growing compounding market continue to be meeting USP, cGMP, and other guidelines to promote patient and compounding pharmacist safety.