» DRUG DELIVERY
» Table 1. PLA/PLGA-based drug products that are available in the U.S.
Drug Product Active Ingredient Dosage Form, Route of Administration
Vivitrol Zoladex Naltrexone Goserelin acetate Strength, Microsphere, Intramuscular 380 mg every 4-weeks Implant, Subcutaneous
3.6 mg or 10.8 mg every 28 days
Approval Date(s), Indication(s)
1984, Indicated for the treatment of alcohol dependence
1989 (3.6 mg), 1996 (10.8 mg), Indicated for use in combination with fl utamide for the management of locally confi ned Stage T2b-T4 carcinoma of the prostate
Lupron Depot
Leuprolide acetate Microsphere, Intramuscular 7.5 mg, every month 22.5 mg, every 3-months 30 mg, every 4-months 45 mg, every 6-months
Lupron Depot-PED Leuprolide acetate Microsphere, Intramuscular 7.5 mg, 11.25 mg, or 15 mg every month 11.25 mg or 30 mg every 3-months
Lupron Leuprolide acetate Microsphere, Intramuscular 3.75 mg, every month Sandostatin LAR Octreotide
Microsphere, Subcutaneous 10 mg, 20 mg, or 30 mg every 4-weeks
1989, Indicated for palliative treatment of advanced prostatic cancer
Characteristics of PLA/PLGA (described in product labeling)
PLGA, L/G: 75/25
PLGA (13.3-14.3 mg/dose) No characterization information
7.5 mg: PLGA (66.2 mg/dose) 22.5 mg: PLA (198.6 mg/dose) 30 mg: PLA (264.8 mg/dose) 45 mg: PLA (169.9 mg/dose) No characterization information
1993, Indicated for the treatment of children with central precocious puberty (CPP)
1995, Indicated for management of endometriosis
1998, Indicated for acromegaly, severe diarrhea/fl ushing episodes associated with metastatic carcinoid tumors, profuse watery diarrhea associated with VIP-secreting tumors
Atridox Doxycycline hyclate
In situ forming gel Periodontal
50 mg
1998, Indicated for the treatment of chronic adult periodontitis for a gain in clinical attachment, reduction in probing depth, and reduction in bleeding on probing
Trelstar Arestin Eligard
Triptorelin pamoate Microsphere, Intramuscular 3.75 mg every 4-weeks 11.25 mg every 12-weeks 22.5 mg every 24-weeks
Minocycline HCl Leuprolide acetate
Microsphere, Periodontal 1 mg, variable dosing frequency
In situ forming gel, Subcutaneous
7.5 mg every month 22.5 mg every 3-months 30 mg every 4-months 45 mg every 6-months
Risperdal Consta Risperidone Ozurdex Bydureon Lupaneta Pack Dexamethasone Exenatide
Leuprolide acetate; Norethindrone acetate
Signifor LAR
Microsphere, Intramuscular 12.5 mg, 25 mg, 37.5 mg, or 50 mg every 2-weeks
Microsphere, Subcutaneous 0.7 mg, variable dosing frequency
Microsphere; Tablet Intramuscular; Oral 2 mg, every 7-days
3.75 mg every month; 5 mg daily
Pasireotide pamoate Microsphere, Intramuscular 20 mg, 40 mg, or 60 mg every 28-days
2000 (3.75 mg), 2001 (11.25 mg), 2010 (22.5 mg), Indicated for the palliative treatment of advanced prostate cancer
2001, Indicated as an adjunct to scaling and root planning procedures in patients with adult periodontitis
2002 (7.5 mg and 22.5 mg), 2003 (30 mg), and 2004 (45 mg), Indicated for the palliative treatment of advanced prostate cancer
2003, Indicated for the treatment of schizophrenia and bipolar I disorder
2009, Indicated for the treatment of macular edema, non-infectious uveitis, and diabetic macular edema
2012, Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes
2012, Indicated for initial management of the painful symptoms of endometriosis and management of recurrence of symptoms
2014, Indicated for the treatment of patients with acromegaly
7.5 mg, 11.25 mg, and 15 mg: PLGA (66.2/99.3/132.4 mg/dose)
11.25 mg and 30 mg: PLA (99.3/264.8 mg/dose) No characterization information
PLGA (33.1 mg/dose) No characterization information
10 mg, 20 mg, and 30 mg: glucose star polymer, PLGA (188.8/377.6/566.4 mg/dose)
PLA (36.7%/dose) No characterization data
3.75 mg, 11.25 mg, and 22.5 mg: PLGA (136/118/182 mg/dose) No characterization information
PLGA No characterization information
7.5 mg: PLGA (82.5 mg/dose), carboxyl endgroups, L/G: 50/50 22.5 mg and 30 mg: PLGA (158.6/211.5 mg/ dose), copolymer with hexanediol, L/G: 75/25 45 mg: PLGA (165 mg/dose), copolymer with hexanediol, L/G: 85/15
12.5 mg, 25 mg, 37,5 mg, and 50 mg: PLGA, L/G: 72/25
PLGA No characterization information PLGA (37.2 mg/dose), L/G: 50/50
DL-lactic and glycolic acids copolymer (33.1 mg), no characterization data
20 mg, 40 mg, and 60 mg: a mixture of two PLGAs per dose PLGA I (26.29/52.58/78.87 mg/dose), L/G: 50-60/40-50 PLGA II (26.29/52.58/78.87 mg/dose), L/G: 50/50
Moreover, even with Q1/Q2 sameness, bioequivalence between the test and reference products cannot be ensured, as diff erences in manufacturing processes may cause diff erences in physicochemical characteristics of the test product and subsequently aff ect drug release behavior and bioavailability. In vitro drug release testing in combination
16 | | May/June 2016
with other characterization studies can be used to evaluate diff erences of the drug product caused by diff erences in PLA/PLGA properties and/or manufacturing processes. However, to date, compendial or biorelevant in vitro drug release assays and relevant characterization studies for PLA/PLGA-based drug products are still lacking.
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