RESUMO

Our research group has pioneered the development of liquisolid pellets as a new drug delivery system targeting at the improvement of the dissolution rates of poorly water-soluble drugs, combining the technological and biopharmaceutical advantages of both multiparticulate and liquisolid systems. Recently, Lam and collaborators claimed the invention of "liqui-pellets" as "the emerging next-generation oral dosage form which stems from liquisolid concept in combination with pelletization technology". However, the concept of liqui-pellet is not novel. As we demonstrate in this commentary, liqui-pellets are the same type of preparation as our previously and extensively reported liquisolid pellets. Liquisolid pellets have been disclosed in a patent application and public peer-reviewed articles covering the concept, preparation and challenges associated with these systems. There are no technical differences that justify excluding our previous reports as the first reports on liquisolid pellets or liqui-pellets. This commentary highlights the similarities between liquisolid pellets and liqui-pellets, focusing on the anteriority of liquisolid pellets as disclosed by our group.

Assuntos

RESUMO

Liquisolid pellets (LPs) prepared by extrusion-spheronization are promising delivery systems to improve the dissolution rate of poorly water-soluble drugs. However, developing LPs for high dose drugs (e.g. antiretroviral ritonavir, RTV) is a major challenge due to technical and quality constraints. In this study, formulations LP1 and LP2 were obtained (RTV 100 mg/unit dose) using microcrystalline cellulose (carrier), Kollidon® CL-SF (coating and disintegrating material) and high load (30%, w/w) of Kolliphor® EL or PEG 400 (non-volatile solvent). LP1 and LP2 had narrow size distribution, good morphological properties, and excellent flowability. The partial conversion of RTV polymorph I to the less soluble form II occurred during the preparation of the liquid medications. LP1 (containing Kolliphor® EL) achieved 82.64 ±â€¯2.17% of drug dissolved in 30 min (Q30min), compared with 53.14 ±â€¯0.6% and 42.42 ±â€¯2.09% for LP2 (containing PEG 400) and Norvir® tablets, respectively. Also, LP1 promoted 1.9-fold/1.7-fold and 8.19-fold/8.29-fold increases in Q30min/DE60min (dissolution efficiency) as compared to neat RTV polymorphs I and II, respectively.

RESUMO

Mini-tablets are a new tendency in solid dosage form design for overcoming therapeutic obstacles such as impaired swallowing and polypharmacy therapy. Among their advantages, these systems offer therapeutic benefits such as dose flexibility and combined drug release patterns. The use of lipids in the formulation has also drawn considerable interest as means to modify the drug release from the dosage form. Therefore, this paper aimed at developing sustained release mini-tablets containing the highly soluble drugs captopril and metformin hydrochloride. Carnauba wax was used as a lipid component in melt granulation, targeting the improvement of the drugs poor flowability and tabletability, as well as to sustain the drug release profiles in association with other excipients. To assist sustaining the drug release, Ethocel™ (EC) and Kollicoat® SR 30D associated with Opadry® II were employed as matrix-forming and reservoir-forming materials, respectively. The neat drugs, granules and the bulk formulations were evaluated for their angle of repose, compressibility index, Hausner ratio and tabletability. Mini-tablets were evaluated for their weight variation, hardness, friability, drug content and in-vitro drug release. The results indicated that melt granulation with carnauba wax improved the flow and the tabletability of the drugs, allowing the preparation of mini-tablets with adequate tensile strength under reduced compaction pressures. All mini-tablet formulations showed acceptable hardness (within the range of 1.16 to 3.93Kp) and friability (<0.1%). The melt-granulated captopril in matrix systems containing 50% EC (45P, 100P or 100FP) and the melt-granulated metformin hydrochloride in reservoir systems coated with Kollicoat® SR 30D and Opadry® II (80:20 with 10% weight gain or 70:30 with 20% weight gain) exhibited release profiles adequate to sustained release formulations, for over 450min. Therefore, carnauba wax proved to be a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of soluble drugs.

Assuntos