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      Design of a gelatin microparticle-containing self-microemulsifying formulation for enhanced oral bioavailability of dutasteride

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          Abstract

          In this study, a gelatin microparticle-containing self-microemulsifying formulation (SMF) was developed using a spray-drying method to enhance the oral delivery of the poorly water-soluble therapeutic dutasteride. The effect of the amount of gelatin and the type and amount of hydrophilic additives, namely, Gelucire ® 44/14, poloxamer 407, sodium lauryl sulfate, Soluplus ®, Solutol™ HS15, and D-α-tocopheryl polyethylene glycol 1000 succinate, on the droplet size, dissolution, and oral absorption of dutasteride from the SMF was investigated. Upon dispersion of the gelatin microparticle-containing SMF in water after spray-drying, the mean droplet size of the aqueous dispersion was in the range of 110–137 nm. The in vitro dissolution and recrystallization results showed that gelatin could be used as a solid carrier and recrystallization inhibitor for the SMF of dutasteride. Furthermore, combination of the gelatin microparticle-containing SMF and Soluplus enhanced the dissolution properties and oral absorption of dutasteride. The results of our study suggest that the gelatin microparticle-containing SMF in combination with Soluplus could be useful to enhance the oral absorption of dutasteride.

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          Most cited references 25

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          Development of solid self-emulsifying drug delivery systems: preparation techniques and dosage forms.

          Approximately 40% of new chemical entities exhibit poor aqueous solubility and present a major challenge to modern drug delivery system, because of their low bioavailability. Self-emulsifying drug delivery systems (SEDDS) are usually used to improve the bioavailability of hydrophobic drugs. Conventional SEDDS, however, are mostly prepared in a liquid form, which can produce some disadvantages. Accordingly, solid SEDDS (S-SEDDS), prepared by solidification of liquid/semisolid self-emulsifying (SE) ingredients into powders, have gained popularity. This article gives an overview of the recent advances in the study of S-SEDDS, especially the related solidification techniques and the development of solid SE dosage forms. Finally, the existing problems and the possible future research directions in this field are pointed out.
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            Solid self-microemulsifying dispersible tablets of celastrol: formulation development, charaterization and bioavailability evaluation.

            The aims of this study were to choose a suitable adsorbent of self-microemulsion and to develop a fine solid self-microemulsifying dispersible tablets for promoting the dissolution and oral bioavailability of celastrol. Solubility test, self-emulsifying grading test, droplet size analysis and ternary phase diagrams test were performed to screen and optimize the composition of liquid celastrol self-microemulsifying drug delivery system (SMEDDS). Then microcrystalline cellulose KG 802 was added as a suitable adsorbent into the optimized liquid celastrol-SMEDDS formulation to prepare the dispersible tablets by wet granulation compression method. The optimized formulation of celastrol-SMEDDS dispersible tablets was finally determinated by the feasibility of the preparing process and redispersibility. The in vitro study showed that the dispersible tablets could disperse in the dispersion medium within 3 min with the average particle size of 25.32 ± 3.26 nm. In vivo pharmacokinetic experiments of rats, the relative bioavailability of celastrol SMEDDS and SMEDDS dispersible tablets compared to the 0.4% CMC-Na suspension was 569 ± 7.07% and 558 ± 6.77%, respectively, while there were no significant difference between the SMEDDS and SMEDDS dispersible tablets. The results suggest the potential use of SMEDDS dispersible tablets for the oral delivery of poorly water-soluble terpenes drugs, such as celastrol.
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              Using polymeric precipitation inhibitors to improve the absorption of poorly water-soluble drugs: A mechanistic basis for utility.

              The inclusion of certain polymers within solid dispersion or lipid-based formulations can maintain drug supersaturation after dispersion and/or digestion of the vehicle, leading to improvements in bioavailability and variability in exposure. This review presents an overview of the fundamental principles that underpin drug precipitation mechanisms, describes the mechanisms by which precipitation may be inhibited, discusses the methods that can be used to identify polymeric precipitation inhibitors (PPIs), and summarizes current literature evidence of the most effective PPIs. Preliminary data from our laboratory is also presented, which describes the precipitation inhibition behavior of 53 polymeric materials using supersaturated solutions of danazol as a model, poorly water-soluble drug. These studies identify a group of PPIs with superior precipitation inhibition qualities, the majority of which are cellulose-based. These new results in combination with previous published data indicate that PPIs represent an appealing new technology with the potential to improve drug absorption for poorly water-soluble drugs. The molecular determinants of polymer utility, however, remain relatively poorly understood, although the cellulose derivates appear, in general, to provide the most benefit. More detailed studies are therefore required to define the parameters that most effectively predict and quantify the drug-polymer relationships that control precipitation inhibition.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2015
                23 June 2015
                : 9
                : 3231-3238
                Affiliations
                [1 ]College of Pharmacy, Kyungsung University, Busan, Republic of Korea
                [2 ]College of Pharmacy, Pusan National University, Busan, Republic of Korea
                Author notes
                Correspondence: Min-Soo Kim, College of Pharmacy, Pusan National University, 2 Busandaehak-ro 63beon-gil, Geumjeong-gu, Busan 609-735, Republic of Korea, Tel +82 51 510 2813, Fax +82 51 513 6754, Email minsookim@ 123456pusan.ac.kr
                [*]

                These authors contributed equally to this work

                Article
                dddt-9-3231
                10.2147/DDDT.S86458
                4484659
                © 2015 Baek et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine

                dissolution, solubility, bioavailability, dutasteride

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