Flow-through cell-based in vitro release method for triamcinolone acetonide poly (lactic-co-glycolic) acid microspheres

Tipnis, Namita; Shen, Jie; Jackson, Derek; Leblanc, Daniel; Burgess, Diane J.

doi:10.1016/j.ijpharm.2020.119130

Cited by 16 publications

(8 citation statements)

References 16 publications

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“…These differences in systemic exposure, which could portend an improved systemic safety profile with TA-ER over TAcs are likely due to the differences in TA formulation. Whereas crystals of TA from the TAcs formulation completely dissolve in under 2 h, less than 1% of the embedded TA is released from the TA-ER microsphere formulation during the same time period and under the same in vitro conditions [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Safety and Systemic Exposure of Triamcinolone Acetonide Following Ultrasound-Guided Intra-Articular Injection of Triamcinolone Extended-Release or Standard Triamcinolone Acetonide in Patients with Shoulder Osteoarthritis: An Open-Label, Randomized Study

et al. 2021

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Background and Objectives Osteoarthritis (OA) is a major public health burden. While knee and hip joints are most commonly affected, the glenohumoral (shoulder) joint is also frequently involved. We evaluated the pharmacokinetics and safety/tolerability of triamcinolone acetonide extended-release (TA-ER) and triamcinolone acetonide crystalline suspension (TAcs) in patients with shoulder OA. Methods In this phase 2, randomized, open-label, single-dose study (NCT03382262), adults with moderately-to-severely symptomatic shoulder OA for ≥ 6 months randomly received a single ultrasound-guided intra-articular (IA) injection of TA-ER 32 mg or TAcs 40 mg. Safety was evaluated throughout 12 weeks post-injection; blood samples for pharmacokinetic evaluations were collected pre-injection and through Day 85 post-injection. Results Among 25 randomized patients, 12 received TA-ER and 13 received TAcs. Most patients were female (60%), and all had moderate (72%) or severe (28%) shoulder OA. Adverse events (AEs) were reported by four (33%) patients following TA-ER and three (23%) following TAcs injection. No AE was serious or led to study discontinuation. Systemic exposure following TAcs was approximately 1.5-fold higher than that following TA-ER injection (geometric mean [GM] AUC 0–last 873,543 vs 557,602 h × pg/mL). GM C max was also higher in TAcs- than TA-ER-treated patients (2034 vs 1283 pg/mL). Bioequivalence testing confirmed lower systemic TA exposure following TA-ER than TAcs IA injection. Conclusion These pharmacokinetic data confirm protracted release of TA from TA-ER following IA injection in patients with shoulder OA. Lower peak and systemic TA exposure following TA-ER suggests TA-ER could potentially confer an improved systemic safety profile over TAcs. Trial Registration Number NCT03382262 (December 22, 2017 retrospectively registered).

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Section: Discussionmentioning

confidence: 99%

Safety and Systemic Exposure of Triamcinolone Acetonide Following Ultrasound-Guided Intra-Articular Injection of Triamcinolone Extended-Release or Standard Triamcinolone Acetonide in Patients with Shoulder Osteoarthritis: An Open-Label, Randomized Study

et al. 2021

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“…This is because the release kinetics of poorly soluble drugs is slower at elevated temperatures [ 29 , 30 , 31 ]. It has been postulated that PLGA plasticisation occurs at elevated temperatures, resulting in the closure of the microspheres’ internal channels and surface pores [ 32 ]. The elevated temperature also facilitates drug recrystallisation within the microspheres.…”

Section: Lack Of a Standard Compendial Methods For In Vitro Release S...mentioning

confidence: 99%

Challenges and Complications of Poly(lactic-co-glycolic acid)-Based Long-Acting Drug Product Development

Lim

Tan

et al. 2022

Pharmaceutics

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Poly(lactic-co-glycolic acid) (PLGA) is one of the preferred polymeric inactive ingredients for long-acting parenteral drug products that are constituted of complex formulations. Despite over 30 years of use, there are still many challenges faced by researchers in formulation-related aspects pertaining to drug loading and release. Until now, PLGA-based complex generic drug products have not been successfully developed. The complexity in developing these generic drug products is not just due to their complex formulation, but also to the manufacturing process of the listed reference drugs that involve PLGA. The composition and product attributes of commercial PLGA formulations vary with the drugs and their intended applications. The lack of standard compendial methods for in vitro release studies hinders generic pharmaceutical companies in their efforts to develop PLGA-based complex generic drug products. In this review, we discuss the challenges faced in developing PLGA-based long-acting injectable/implantable (LAI) drug products; hurdles that are associated with drug loading and release that are dictated by the physicochemical properties of PLGA and product manufacturing processes. Approaches to overcome these challenges and hurdles are highlighted specifically with respect to drug encapsulation and release.

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“…In vitro release test was performed using the sample-and-separate method as previously reported . OL-M (20 mg) or equivalent OL-M/Gel was immersed in 5 mL of PBS (pH 7.4) with 0.25% SDS and incubated at 37 °C under constant agitation.…”

Section: Methodsmentioning

confidence: 99%

Localized Microsphere/Hydrogel for Tumor Immunotherapy of Cardiac Glycoside with Minimal Toxicity

Gao

Zhao

Mao

et al. 2022

ACS Appl. Mater. Interfaces

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It has been reported that cardiac glycosides (CGs) commonly used in clinical practice can inhibit tumor growth by inducing immunogenic cell death (ICD), and their positive benefits have been documented in several clinical trials of drug combinations. However, the inherent cardiogenic side effects need to be addressed before CGs can be truly applied in clinical antitumor therapy. In this study, a dual controlled release microsphere/hydrogel platform (OL-M/Gel) was constructed to precisely control the output of oleandrin (OL, one of the representative CGs) in situ in tumors. With the help of this intelligent drug release platform, OL can be released in vitro and in vivo in a sustained and stable manner. The ability of OL to induce ICD and the subsequent antigen presentation and cytotoxic T-cell cascades was first stated, which resulted in potent tumor growth suppression without significant side effects. In addition, the inhibition of autologous tumor recurrence and metastasis by OL-M/Gel was also revealed. This study is expected to break through the inherent bottleneck of CGs and promote their clinical transformation in the field of antitumor treatment.

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Flow-through cell-based in vitro release method for triamcinolone acetonide poly (lactic-co-glycolic) acid microspheres

Cited by 16 publications

References 16 publications

Safety and Systemic Exposure of Triamcinolone Acetonide Following Ultrasound-Guided Intra-Articular Injection of Triamcinolone Extended-Release or Standard Triamcinolone Acetonide in Patients with Shoulder Osteoarthritis: An Open-Label, Randomized Study

Safety and Systemic Exposure of Triamcinolone Acetonide Following Ultrasound-Guided Intra-Articular Injection of Triamcinolone Extended-Release or Standard Triamcinolone Acetonide in Patients with Shoulder Osteoarthritis: An Open-Label, Randomized Study

Challenges and Complications of Poly(lactic-co-glycolic acid)-Based Long-Acting Drug Product Development

Localized Microsphere/Hydrogel for Tumor Immunotherapy of Cardiac Glycoside with Minimal Toxicity

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