Pharmacokinetics and Preformulation

Mittal, Bhavishya

doi:10.1016/b978-0-12-804731-6.00002-9

Cited by 8 publications

(9 citation statements)

References 3 publications

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“…There are several physicochemical properties of a drug that may impact release kinetics, such as solubility. Solubility in this context refers to a drug’s maximum capacity to dissolve into the solution surrounding the device (typically an aqueous solution) at equilibrium and is dependent on its polymorphic form and polarity [ 138 , 139 ]. It is known that a concentration gradient typically drives diffusion, but it is also a function of solubility; a drug with higher solubility typically results in faster release and wider distribution if placed in an aqueous environment.…”

Section: Drug Properties On Release Kineticsmentioning

confidence: 99%

Design of Biopolymer-Based Interstitial Therapies for the Treatment of Glioblastoma

Pena

Graham-Gurysh

Bachelder

et al. 2021

IJMS

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Glioblastoma multiforme (GBM) is the most common form of primary brain cancer and has the highest morbidity rate and current treatments result in a bleak 5-year survival rate of 5.6%. Interstitial therapy is one option to increase survival. Drug delivery by interstitial therapy most commonly makes use of a polymer implant encapsulating a drug which releases as the polymer degrades. Interstitial therapy has been extensively studied as a treatment option for GBM as it provides several advantages over systemic administration of chemotherapeutics. Primarily, it can be applied behind the blood–brain barrier, increasing the number of possible chemotherapeutic candidates that can be used and reducing systemic levels of the therapy while concentrating it near the cancer source. With interstitial therapy, multiple drugs can be released locally into the brain at the site of resection as the polymer of the implant degrades, and the release profile of these drugs can be tailored to optimize combination therapy or maintain synergistic ratios. This can bypass the blood–brain barrier, alleviate systemic toxicity, and resolve drug resistance in the tumor. However, tailoring drug release requires appropriate consideration of the complex relationship between the drug, polymer, and formulation method. Drug physicochemical properties can result in intermolecular bonding with the polymeric matrix and affect drug distribution in the implant depending on the formulation method used. This review is focused on current works that have applied interstitial therapy towards GBM, discusses polymer and formulation methods, and provides design considerations for future implantable biodegradable materials.

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Section: Drug Properties On Release Kineticsmentioning

confidence: 99%

Design of Biopolymer-Based Interstitial Therapies for the Treatment of Glioblastoma

Pena

Graham-Gurysh

Bachelder

et al. 2021

IJMS

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“…It is well known that drug molecules have to be released from the matrix of the pharmaceutical dosage form and then, dissolve in order to be absorbed and to cause the intended therapeutic effect. Nevertheless, both processes are greatly dependent on the physicochemical properties of the API, and the ones from the excipients as well [ 137 ]. Consequently, Göke et al state that poor water solubility is one of the major pharmaceutical challenges for drug development [ 138 ].…”

Section: Drug Development Through Electrospun Nanofibersmentioning

confidence: 99%

Electrospun nanofibers: A nanotechnological approach for drug delivery and dissolution optimization in poorly water-soluble drugs

et al. 2020

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<p class="ADMETabstracttext">Electrospinning is a novel and sophisticated technique for the production of nanofibers with high surface area, extreme porous structure, small pore size, and surface morphologies that make them suitable for biomedical and bioengineering applications, which can provide solutions to current drug delivery issues of poorly water-soluble drugs. Electrospun nanofibers can be obtained through different methods asides from the conventional one, such as coaxial, multi-jet, side by side, emulsion, and melt electrospinning. In general, the application of an electric potential to a polymer solution causes a charged liquid jet that moves downfield to an oppositely charged collector, where the nanofibers are deposited. Plenty of polymers that differ in their origin, degradation character and water affinity are used during the process. Physicochemical properties of the drug, polymer(s), and solvent systems need to be addressed to guarantee successful manufacturing. Therefore, this review summarizes the recent progress in electrospun nanofibers for their use as a nanotechnological tool for dissolution optimization and drug delivery systems for poorly water-soluble drugs.</p>

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“…In order to obtain the desired in vivo performance of aqueous suspensions, physicochemical properties and physiological parameters are important to consider when developing these formulations. , Some excipients have an influence on drug absorption and, hence, bioavailability. For instance, stabilizing excipients are often chosen based on their stabilizing effect in the aqueous suspension, which results in maintaining long-term physical stability .…”

Section: Introductionmentioning

confidence: 99%

Linking In Vitro Intrinsic Dissolution Rate and Thermodynamic Solubility with Pharmacokinetic Profiles of Bedaquiline Long-Acting Aqueous Microsuspensions in Rats

et al. 2021

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Pharmacokinetic (PK) profiles of a range of bedaquiline (BDQ) long-acting injectable (LAI) microsuspensions in rats after parenteral (i.e., intramuscular and subcutaneous) administration were correlated with the in vitro intrinsic dissolution rate (IDR) and thermodynamic solubility of BDQ in media varying in surfactant type and concentration to better understand the impact of different nonionic surfactants on the in vivo performance of BDQ LAI microsuspensions. All LAI formulations had a similar particle size distribution. The investigated surfactants were d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), poloxamer 338, and poloxamer 188. Furthermore, the relevance of medium complexity by using a biorelevant setup to perform in vitro measurements was assessed by comparing IDR and thermodynamic solubility results obtained in biorelevant media and formulation vehicle containing different surfactants in varying concentrations. In the presence of a surfactant, both media could be applied to obtain in vivo representative dissolution and solubility data because the difference between the biorelevant medium and formulation vehicle was predominantly nonsignificant. Therefore, a more simplistic medium in the presence of a surfactant was preferred to obtain in vitro measurements to predict the in vivo PK performance of LAI aqueous suspensions. The type of surfactant influenced the PK profiles of BDQ microsuspensions in rats, which could be the result of a surfactant effect on the IDR and/or thermodynamic solubility of BDQ. Overall, two surfactant groups could be differentiated: TPGS and poloxamers. Most differences between the PK profiles (i.e., maximum concentration observed, time of maximum concentration observed, and area under the curve) were observed during the first 21 days postdose, the time period during which particles in the aqueous suspension are expected to dissolve.

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Pharmacokinetics and Preformulation

Cited by 8 publications

References 3 publications

Design of Biopolymer-Based Interstitial Therapies for the Treatment of Glioblastoma

Design of Biopolymer-Based Interstitial Therapies for the Treatment of Glioblastoma

Electrospun nanofibers: A nanotechnological approach for drug delivery and dissolution optimization in poorly water-soluble drugs

Linking In Vitro Intrinsic Dissolution Rate and Thermodynamic Solubility with Pharmacokinetic Profiles of Bedaquiline Long-Acting Aqueous Microsuspensions in Rats

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