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» 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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