Issue link: https://www.e-digitaleditions.com/i/883179
market have THC-to-CBD ratios tailored to offer certain effects or meet specific indications. Ratios such as 1-to-1 or 1-to-15 are thought to offer benefits for certain indica- tions or prevent psychoactive effects while remaining effective. If local regulations allow, you can add crystalline CBD to a liquid capsule formulation or to a powder for- mulation for tablets. Doing so enables you to achieve a precise cannabinoid profile. Other strategies for achieving the desired ratio involve mixing oils with different THC- to-CBD profiles. The ratios of cannabinoids in oils made using SFE are mostly a function of the raw material, that is, the genetics of particular strains of plants. CBD has been clinically proven to mediate certain conditions, including seizures from epilepsy. One strain of cannabis, Charlotte's Web, has become widely known for its high-CBD/low-THC content and has been used to prevent seizures in children diagnosed with drug-resistant forms of epilepsy. Isolation and purification of lesser-used cannabinoids, such as tetrahydrocannabivarin (THCV), require sophisticated chromatographic separation tech- niques. These techniques are becoming more popular in mature markets, where it's difficult to formulate a unique product that stands out in the market place. Good science Anyone who has dealt with natural products, be it an API or excipient, knows that inherent variation in these materials is a given. Cannabinoids are no different and because their properties are in flux, a robust formulation design is mandatory. In fact, I believe that's always mandatory, but poor formulations persist, as they have since I got my start nearly 30 years ago. While I'm no fan of extra regulations and bureaucracy, I approve of the FDA's push into Quality by Design (QbD) in formulating pharmaceuticals. Today, I'm not bound by FDA regula- tions, but my colleagues and I still practice QbD. I call it good science and common sense: Learn where the issues lie and don't operate in a space where your formulation can fail. That's what we do at PharmaCann, which is a vertically integrated company. We grow our own plant stock, extract the API, and make the finished products. When formulating natural products, that can be an advantage because the control we have enables us to tai- lor the API to a specific formulation. Beyond solid dosage There is a variety of cannabis products that aren't tablets or capsules in both the medical and recreational markets. As a medicine, cannabis is available only with a recommendation or prescription from a physician. In recreational markets, anyone can get cannabis. Both mar- kets have standards for impurities and residual chemicals, such as pesticides and hydrocarbons. Edibles are very popular in the recreational market but require significant dosing due to the pharmacology of cannabinoids. Most other products, regardless of the market, are liquids and include tinctures, sublingual sprays, and "vape" cartridges. Inhalation is probably still the most popular method of taking cannabis. Many people smoke the flowers, but that is not an option for some patients. As with tobacco, many people opt not to inhale smoke into their lungs, even though inhalation offers the most rapid onset and makes it easy to control dosing. That's why vaping— inhaling the vapor emitted from heated oil formula- tions—is a popular alternative to smoking. SEDDS-based products and liposome-based sublingual sprays also pro- vide rapid onset. A word about regulations Cannabinoid regulations are complicated because every state has its own rules. Federal law prohibits the transport of cannabinoids across state lines, so any com- pany that plans to reach markets beyond its home state must install production equipment locally. It is not possi- ble to manufacture and distribute from a central facility. As a result, manufacturers must build a suite in each state they seek to serve. This can get expensive fast because it means buying five production-scale encapsula- tion machines instead of one. In addition, not all markets embrace all dosage forms, and it's the customer who ulti- mately dictates what products get formulated and what they include. I'll conclude with this fact: From 1911 to 1933, more than half the states in the USA passed laws banning cannabis. But the federal government took no action over that period. Today, the same states that were first to ban cannabis are the first to legalize it and many allow a recre- ational market even while a federal ban remains. T&C References 1. Jarho P, Pate DW, Brenneisen R, Järvinen T. Hydroxypropyl-beta-cyclodextrin and its combination with hydroxypropyl-methylcellulose increases aqueous solubility of delta9-tetrahydrocannabinol. Life Sci. 1998;63(26):PL381-4. 2. Ben-Shabat S, Sheskin, T, Tamiri, T, Rhee, MH, Vogel Z, Bisogno T, De Perocellis L, Di Marzo V, Mechoulam R. An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glyc- erol cannabinoid activity. Eur J Pharmacol. 1998 Jul 17;353(1):23-31. David Schaible is the senior product development and formu- lating chemist at PharmaCann. E-mail: david.schaible@phar macannis.com. Prior to his work in cannabis, Schaible spent more than 25 years in the generic, drug delivery, and excipient industries. He has been invited to speak domestically and abroad about excipients and cannabis. He holds several patents and is the author of several articles, posters, and papers. 30 October 2017 Tablets & Capsules