Tags

Type your tag names separated by a space and hit enter

Encapsulation of poorly soluble basic drugs into enteric microparticles: a novel approach to enhance their oral bioavailability.
Int J Pharm. 2011 Sep 15; 416(1):55-60.IJ

Abstract

Poorly water soluble basic drugs are very sensitive to pH changes and following dissolution in the acidic stomach environment tend to precipitate upon gastric emptying, which leads to compromised or erratic oral bioavailability. In this work, we show that the oral bioavailability of a model poorly soluble basic drug (cinnarizine) can be improved by drug encapsulation within highly pH-responsive microparticles (Eudragit L). The latter was prepared by emulsion solvent evaporation which yielded discrete spherical microparticles (diameter of 56.4±6.8μm and a span of 1.2±0.3). These Eudragit L (dissolution threshold pH 6.0) microparticles are expected to dissolve and release their drug load at intestinal conditions. Thus, the enteric microparticles inhibited the in vitro release of drug under gastric conditions, despite high cinnarizine solubility in the acidic medium. At intestinal conditions, the particles dissolved rapidly and released the drug which precipitated out in the dissolution vessel. In contrast, cinnarizine powder showed rapid drug dissolution at low pH, followed by precipitation upon pH change. Oral dosing in rats resulted in a greater than double bioavailability of Eudragit L microparticles compared to the drug powder suspension, although C(max) and T(max) were similar. The higher bioavailability with microparticles contradicts the in vitro results. Such an example highlights that although in vitro results are an indispensable tool for formulation development, an early in vivo assessment of formulation behaviour can provide better prediction for oral bioavailability.

Links

Publisher Full Text
Aggregator Full Text

Authors+Show Affiliations

Alhnan MA
Department of Pharmaceutics, University of London, London WC1N 1AX, UK.
Murdan S
No affiliation info available
Basit AW
No affiliation info available

MeSH

Administration, OralAnimalsBiological AvailabilityCinnarizineDrug CompoundingHydrogen-Ion ConcentrationIn Vitro TechniquesMaleParticle SizePolymethacrylic AcidsRatsRats, WistarSolubilityTablets, Enteric-Coated

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21679756

Citation

Alhnan, Mohamed A., et al. "Encapsulation of Poorly Soluble Basic Drugs Into Enteric Microparticles: a Novel Approach to Enhance Their Oral Bioavailability." International Journal of Pharmaceutics, vol. 416, no. 1, 2011, pp. 55-60.
Alhnan MA, Murdan S, Basit AW. Encapsulation of poorly soluble basic drugs into enteric microparticles: a novel approach to enhance their oral bioavailability. Int J Pharm. 2011;416(1):55-60.
Alhnan, M. A., Murdan, S., & Basit, A. W. (2011). Encapsulation of poorly soluble basic drugs into enteric microparticles: a novel approach to enhance their oral bioavailability. International Journal of Pharmaceutics, 416(1), 55-60. https://doi.org/10.1016/j.ijpharm.2011.05.079
Alhnan MA, Murdan S, Basit AW. Encapsulation of Poorly Soluble Basic Drugs Into Enteric Microparticles: a Novel Approach to Enhance Their Oral Bioavailability. Int J Pharm. 2011 Sep 15;416(1):55-60. PubMed PMID: 21679756.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Encapsulation of poorly soluble basic drugs into enteric microparticles: a novel approach to enhance their oral bioavailability. AU - Alhnan,Mohamed A, AU - Murdan,Sudaxshina, AU - Basit,Abdul W, Y1 - 2011/06/14/ PY - 2011/03/05/received PY - 2011/05/26/revised PY - 2011/05/28/accepted PY - 2011/6/18/entrez PY - 2011/6/18/pubmed PY - 2011/12/28/medline SP - 55 EP - 60 JF - International journal of pharmaceutics JO - Int J Pharm VL - 416 IS - 1 N2 - Poorly water soluble basic drugs are very sensitive to pH changes and following dissolution in the acidic stomach environment tend to precipitate upon gastric emptying, which leads to compromised or erratic oral bioavailability. In this work, we show that the oral bioavailability of a model poorly soluble basic drug (cinnarizine) can be improved by drug encapsulation within highly pH-responsive microparticles (Eudragit L). The latter was prepared by emulsion solvent evaporation which yielded discrete spherical microparticles (diameter of 56.4±6.8μm and a span of 1.2±0.3). These Eudragit L (dissolution threshold pH 6.0) microparticles are expected to dissolve and release their drug load at intestinal conditions. Thus, the enteric microparticles inhibited the in vitro release of drug under gastric conditions, despite high cinnarizine solubility in the acidic medium. At intestinal conditions, the particles dissolved rapidly and released the drug which precipitated out in the dissolution vessel. In contrast, cinnarizine powder showed rapid drug dissolution at low pH, followed by precipitation upon pH change. Oral dosing in rats resulted in a greater than double bioavailability of Eudragit L microparticles compared to the drug powder suspension, although C(max) and T(max) were similar. The higher bioavailability with microparticles contradicts the in vitro results. Such an example highlights that although in vitro results are an indispensable tool for formulation development, an early in vivo assessment of formulation behaviour can provide better prediction for oral bioavailability. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/21679756/Encapsulation_of_poorly_soluble_basic_drugs_into_enteric_microparticles:_a_novel_approach_to_enhance_their_oral_bioavailability_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(11)00531-X DB - PRIME DP - Unbound Medicine ER -