Development of α-Cyclodextrin-Based Orally Disintegrating Tablets for 4-Phenylbutyrate

Today’s cyclodextrin:
One of the greatest features of CDs is that with a proper application (especially when the local CD concentration is relatively high), they can not only improve the solubility but also the permeability of compounds. For example, in the case of a peroral application, let’s say an orally disintegrating tablet. Not to mention that their taste masking potential is also of use in this case. 3 birds with one stone!

In this paper, you can find a great example of such a smart application. If you are interested in developing similar formulations, check out the first steps here: Formulation development – www.carbohydesolutions.com

Pharmaceutics | Free Full-Text | Development of α-Cyclodextrin-Based Orally Disintegrating Tablets for 4-Phenylbutyrate (mdpi.com)

Development of abiraterone acetate tablets with enhanced oral bioavailability

Today’s cyclodextrin
Reading this paper from Yeungnam University by Jong Oh Kim et al reminded me about a core application of CD’s: improving oral bioavailability of compounds. While this feature does not work generally on all compounds, it certainly does on the ones, where the poor solubility is the main cause of the low oral bioavailability. On the other hand, this feature of CD’s often make developing generic drugs with this excipients impossible, while creating improved/added value reformulations of repurposed APIs remains a target use.

If you have projects like this on your table, you might find it useful to check this website: Development of abiraterone acetate tablets with enhanced oral bioavailability | Journal of Pharmaceutical Investigation (springer.com)

Lactic acid bacterium-containing tablets

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.

Lactic acid bacterium-containing tablets on Espacenet

Can the Oral Bioavailability of the Discontinued Prostate Cancer Drug Galeterone Be Improved by Processing Method? KinetiSol® Outperforms Spray Drying in a Head-to-head Comparison

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 GalaDaniel Davis, Sandra KuceraDave A. Miller, & Robert Williams 

Can the Oral Bioavailability of the Discontinued Prostate Cancer Drug Galeterone Be Improved by Processing Method? KinetiSol® Outperforms Spray Drying in a Head-to-head Comparison | SpringerLink


Kit for preparing a medicament, cannabinoid composition, and preparation method

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

See the full patent on Espacenet

Oculis announces positive top-line results from diamond Stage 1 Phase 3 trial in diabetic macular edema with OCS-01 eye drops

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.

See the official annoucement here

Drug complexes: Perspective from Academic Research and Pharmaceutical Market

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 MunnangiAhmed YoussefNagarjuna NaralaPreethi LakkalaSagar NaralaSateesh Kumar Vemula, Ph.D. & Michael Repka  

See the full article here

ɑ-cyclodextrin (A), β-cyclodextrin (B), γ-cyclodextrin (C), Hydroxypropyl-β-cyclodextrin (D), Cucurbit(7)uril (E), Cucurbit(8)uril (F), sulfonatocalix(4)arene (G) & sulfonatocalix(8)arene (H).

Stabilization of cannabis resin and solid oral cannabinoid formulations

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. 

See the patent on Patentscope

Three-in-one: exploration of co-encapsulation of cabazitaxel, bicalutamide and chlorin e6 in new mixed cyclodextrin-crosslinked polymers

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.

Elisabetta Pancani, PharmD, Marco AgnesArianna MazzaAlessandro Venturini et al.

See the full article here

Anomalous Properties of Cyclodextrins and Their Complexes in Aqueous Solutions

today’s cyclodextrin:
This review by Thorsteinn LoftssonHakon 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.

See the full article here: Anomalous Properties of Cyclodextrins and Their Complexes in Aqueous Solutions