Today’s cyclodextrin: This is a little quiz for you. Guess WHY cyclodextrin is added to this formulation! It is a product from Kirin Holdings, a novel lactic acid bacterium-containing tablets that comprises a lactic acid bacterium, an excipient, and a lubricant, wherein the excipient is hydroxypropyl cellulose and/or crystalline cellulose or β-cyclodextrin. The tablets prepared accordingly are claimed to have high intake efficiency and excellent hardness.
Excellent case study by The University of Texas at Austin on improving the bioavailabilty of Galeterone, a novel prostate cancer candidate treatment. KinetiSol(R) compounding was utilized to create galeterone amorphous solid dispersions containing the complexing agent hydroxypropyl-β-cyclodextrin or hypromellose acetate succinate with lower drug loads that both achieved a ~ 6 × increase in dissolution performance versus the 50–50 spray-dried dispersion. When compared to a spray-dried dispersion with an equivalent drug load, the KinetiSol amorphous solid dispersions formulations exhibited ~ 2 × exposure in an in vivo rat study. Urvi Gala, Daniel Davis,Sandra Kucera, Dave A. Miller, & Robert Williams
today’s #cyclodextrin: Vayamed Cannakits® hits the markets: novel formulation kits enabling a cannabis-enriched Nasal Spray, and Vaginal/Rectal Suppositories is now available. This innovation makes Vayamed the first cannabis company in Germany to expand the therapy spectrum with new dosage forms. Depending on the final formulation, the kit contains an excipient mixture composed of vegetable oil, hydroxylated fat, and 2-hydroxypropyl-β-cyclodextrin or polyethylene glycol stearate. Marco Ternelli – Sanity Group
today’s #cyclodextrin: Oculis, a global biopharmaceutical company purposefully driven to save sight and improve eye care, announced positive top line results from Stage 1 of its Phase 3 trial of OCS-01 (dexamethasone formulated in gamma-cyclodextrin #nanoparticles) eye drops in Diabetic Macular Edema (DME). DME is the leading cause of visual loss and legal blindness in patients with diabetes, affecting around 37 million people worldwide, with a significant number of patients left untreated due to a lack of convenient treatment options. OCS-01, in this 3-month trial, has met both clinical efficacy endpoints (main BCVA change, proportion of patients with 3 lines gain) that are required for regulatory approval if met at 12 months treatment duration.
today’s cyclodextrin: Drug complexes: Perspective from Academic Research and Pharmaceutical Market Despite numerous research efforts, drug delivery through the oral route remains a major challenge to formulation scientists. The oral delivery of drugs poses a significant challenge because more than 40% of new chemical entities are practically insoluble in water. Low aqueous solubility is the main problem encountered during the formulation development of new actives and for generic development. A complexation approach has been widely investigated to address this issue, which subsequently improves the bioavailability of these drugs. This review discusses the various types of complexes such as metal complex (drug-metal ion), organic molecules (drug-caffeine or drug-hydrophilic polymer), inclusion complex (drug-cyclodextrin), and pharmacosomes (drug-phospholipids) that improves the aqueous solubility, dissolution, and permeability of the drug along with the numerous case studies reported in the literature. Besides improving solubility, drug-complexation provides versatile functions like improving stability, reducing the toxicity of drugs, increasing or decreasing the dissolution rate, and enhancing bioavailability and biodistribution. Apart, various methods to predict the stoichiometric ratio of reactants and the stability of the developed complex are discussed. Siva Ram Munnangi, Ahmed Youssef, Nagarjuna Narala, Preethi Lakkala, Sagar Narala, Sateesh Kumar Vemula, Ph.D. & Michael Repka
today’s cyclodextrin: using CDs to solubilize and stabilize cannabinoids is very popular in the pharma and nutraceutical/food industries. The most recent paper I read on the topic is from Canntab Therapeutics, yet in the past 25 years, since the first paper from Pekka Jarho et al., we have seen cannabis seed oil stabilized by BCD, an herbal medicine pill for treating constipation, fructus cannabis pill for the treatment of constipation and bowel discomfort, tea for patients in gastric cancer, intestine-lubricating and bowel relaxing granules. Among foods, yogurt enriched with herbal excipients, such as cannabis seeds, and BCD as a health food is claimed useful for soothing nerves, reducing blood pressure and blood fat, dispelling wind-damp, cold, and heat, losing weight, resisting aging, and relaxing bowels. On the analogy of powdered alcohol (Palcohol) prepared by complexing alcoholic drinks with CD, powdered weed, the cyclodextrin-encapsulated cannabinoid is expected to get on the market.
Another great paper comes out of the long-term collaboration between our CSO,Milo Malanga and Ilse Manet‘s lab at National Research Council of Italy. We explored a series of cyclodextrin (CyD) polymers composed either of a single CyD type or a mixture of two CyD types to encapsulate simultaneously different compounds with potential therapeutic interest for multimodal prostate cancer treatment. Thanks to a single inexpensive CyD-based polymer, we produced a three-in-one platform for the future implementation of combined chemotherapy and photodynamic therapy. These achievements are most relevant as nanomedicines are continuously proposed, but their potential for translation to the pharma industry is compromised by their limited potential for industrial upscale.
today’s cyclodextrin: This review by Thorsteinn Loftsson, Hakon Hrafn Sigurdsson, and Phatsawee Jansook pulls a brave topic. It accounts some of the unexpected results the authors have encountered during their studies of CDs as pharmaceutical excipients. CDs are constantly surprising investigators with their unique physicochemical properties. CDs are solubilizing complexing agents of poorly soluble drugs in aqueous solutions, while they can also act as organic cosolvents like ethanol. CDs and their complexes self-assemble in aqueous solutions to form both nano- and microparticles. The nanoparticles have diameters that are well below the wavelength of visible light; thus, the solutions appear to be clear. However, the nanoparticles can result in erroneous conclusions and misinterpretations of experimental results. CDs can act as penetration enhancers, increasing drug permeation through lipophilic membranes, but they do so without affecting the membrane barrier.
today’s #cyclodextrin: achieving controlled release with cyclodextrins can be really challenging, yet it is doable. In fact, there are multiple strategies to get there. In this review, Jana Ghitman and Voicu Stefan Ioan collected different approaches of cyclodextrins-based drug delivery forms that are suitable for co-delivery systems, non-viral vectors for gene delivery, and theranostics. This review presents the latest achievements in nanoparticle-based supramolecular architectures, taking into account the main synthesis methods and the stimuli that control the release (light-responsive, pH-responsive, redox-responsive, and multi-responsive). The review also presents applications and also the present status regarding commercial systems based on cyclodextrins and their characteristics.
This research is close to my heart as it comes from a Hungarian collaboration on developing nepafenac eyedrops with improved absorption. The results showed that one formulation possessed better bioavailability ex vivo than Nevanac® 0.1 % suspension, while the other formulation containing only 60 % of the original dose was ex vivo equivalent with Nevanac® opening the way to nepafenac-containing eye drops with better patient compliance in the future.
