SOLUBILIZING & STABILIZING TECHNOLOGY – CAPTISOL® – Part Perseverance & Part Serendipity

drug delivery, Today's cyclodextrin

today’s cyclodextrin:
The article on Captisol®, a solubilizing and stabilizing technology of Ligand Pharmaceuticals, highlights its evolution from uncertain beginnings to becoming a pharmaceutical industry staple, thanks to the perseverance of scientists and strategic partnerships, notably with Pfizer. Initially developed from the need for better drug formulation tools, Captisol has been integral in creating viable drug products, especially for poorly soluble and unstable molecules. Its proven safety, alongside innovations in production and application, has led to its inclusion in multiple FDA-approved drugs, with ongoing expansion into various administration routes and global regulatory acceptance​​.
#formulationdevelopment #drugdelivery

SOLUBILIZING & STABILIZING TECHNOLOGY – CAPTISOL® – Part Perseverance & Part Serendipity (drug-dev.com)

New Captisol (Ligand Pharmaceuticals) enabled API on the market!

drug delivery, Today's cyclodextrin,

Today’s cyclodextrin:

Eisai Co., Ltd. obtained marketing authorization approval in January 2024 from the Japanese Ministry of Health, Labour and Welfare for the injection formulation of its in-house discovered antiepileptic drug (AED) Fycompa® (perampanel) in Japan as an alternative therapy when oral administration is temporarily not possible. Fycompa is formulated with Captisol®, a Ligand technology.

About perampanel (Fycompa®)
Perampanel is a first-in-class anti-epileptic agent (AED) discovered and developed by Eisai. With epileptic seizures being mediated by the neurotransmitter glutamate, the agent is a highly selective, noncompetitive AMPA receptor antagonist that reduces neuronal hyperexcitation associated with seizures by targeting glutamate activity at AMPA receptors on postsynaptic membranes. Perampanel is currently approved in more than 75 countries and territories, including Japan, China, and other countries in Europe and Asia, as an adjunctive treatment for partial-onset seizures (with or without secondarily generalized seizures) in patients with epilepsy 12 years of age and older. In addition, perampanel has been approved in more than 70 countries, including Japan, Europe, and Asia, for treatment as an adjunctive therapy for primary generalized tonic-clonic seizures in patients with epilepsy 12 years of age and older. In Japan and China, perampanel is approved for monotherapy and adjunctive use in the treatment of partial-onset seizures (with or without secondarily generalized seizures) in patients with epilepsy 4 years of age and older. In Europe, the approved age range is 4 years of age and older for the adjunctive treatment of partial-onset seizures (with or without secondarily generalized seizures) and 7 years of age and older for the treatment as an adjunctive therapy for primary generalized tonic-clonic seizure. A tablet, fine granule formulation, and injection formulation have been approved in Japan. An oral suspension formulation and tablet have been approved in Europe and China. In January 2023, the commercial rights in the United States were transferred to Catalyst Pharmaceuticals, Inc.

Stable, liquid pharmaceutical compositions comprising Melphalan

carbohydrates, , ,

The cyclodextrin-enabled formulation of melphalan is an excellent example of how outdated excipients could be replaced with safer and more effective cyclodextrins to create patient-friendly and superior drug products!
Espacenet – Stable, liquid pharmaceutical compositions comprising melphalan
here you can find similar examples: Formulation development – www.carbohydesolutions.com

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

drug delivery, Today's cyclodextrin

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

drug delivery, Today's cyclodextrin

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,

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

carbohydrates,

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 

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

drug delivery, , ,

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

drug delivery,

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

drug delivery, Today's cyclodextrin,

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  

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).