In Vitro Drug Release

W Im-Emsap, R Bodmeier. In vitro drug release from in situ forming microparticle (ISM)-systems with dispersed drug. AAPS PharmSci Supplement 2(4), AAPS Annual Meeting Abstracts, 2000. 

KS Murthy, RG Reisch, Jr., MB Fawzi. Dissolution stability of hard-shell capsule products. Part II the effect of dissolution test conditions on in vitro drug release. Pharm Technol 13(6) 53-58, 1989. 

KS Murthy, JC Samyn. Effect of shear mixing on in vitro drug release of capsule formulations containing lubricants. J Pharm Sci 66 1215-1219, 1977. 

Lavasanifar, A., Ghalandari, R., Ataei, Z., Zolfaghari, M.E. and Mortazavi, S.A. (1997) Microencapsulation of theophylline using ethylcellulose in vitro drug release and kinetic modelling. Journal of Microencapsulation, 14, 91-100. 

One challenge that remains in biopharmaceutics research is that of correlating in vitro drug-release profiles with the in vivo pharmacokinetic data. TVIVC has been defined by the... 

Figure 2 Simulated in vitro drug-release profiles (panels a and b) and resultant plasma concentration—time profiles for a drug with a 1—hr half-life (panel c) and a 6—hr half-life (panel d).

Table 1 Comparison of Predicted Pharmacokinetic Parameters for Two Different Drugs with Identical In Vitro Drug Release Profiles, But Different Drug Disposition Characteristics (ty2 = 1 or 6 hr)...

Table 2 Fitted Weibull Parameters for the Three In Vitro Drug-Release Profiles Shown in Figure 3...

In order to obtain an in vitro-in vivo relationship two sets of data are needed. The first set is the in vivo data, usually entire blood/plasma concentration profiles or a pharmacokinetic metric derived from plasma concentration profile (e.g., cmax, tmax, AUC, % absorbed). The second data set is the in vitro data (e.g., drug release using an appropriate dissolution test). A mathematical model describing the relationship between these data sets is then developed. Fairly obvious, the in vivo data are fixed. However, the in vitro drug-release profile is often adjusted by changing the dissolution testing conditions to determine which match the computed in vivo-release profiles the best, i.e., results in the highest correlation coefficient. 

For an extended-release dosage form, at least three test time points are chosen to characterize the in vitro drug-release profile for the routine batch-to-batch quality control for approved products. Additional sampling times may be required for formulation development studies, biopharmaceutical evaluations, and drug approval purposes. An early time... 

El Sherbiny IM, Lins RJ, Abdel-Bary EM, Harding DRK (2005) Preparation, characterization, swelling and in vitro drug release behaviour of poly [N-acryloylglycine-chitosan interpoly-meric pH and thermally-responsive hydrogels. European Polymer Journal 41 2584-2591. 

Schneeweis, A., Papantoniou, I., and Mueller-Goymann, C.C., Diclofenac sodium plasma concentrations in dogs after peroral application of soft gelatine capsules enabling application induced transformation (AIT) into a semisolid system of liquid crystals (SSLC) compared to in vitro drug release, Pharm. Pharmacol Lett., 7 42-44 (1997). 

Oral controlled drug-release systems are increasingly used for short half-life drugs to reduce peak blood levels and side-eflfects, to maintain optimum drug concentration and to stimulate patient compliance. In order to maintain a constant blood-level of the drug during an extended period, a constant in vitro drug release rate is desired. The most popular controlled-release system is the matrix tablet (Desai et al., 1965). Te Wierik et al. (1996) reported on... 

Murthy KS, Samyn JC. Effect of shear mixing on in vitro drug release of capsule formulations containing lubricants. J Pharm Sci 1977 66 1215-1219. Nakagawa H. Effects of particle size of rifampicin and addition of magnesium stearate in release of rifampicin from hard gelatin capsules. Yakugaku Zasshi 1980 100 1111-1117. 

Since the Methocel matrix, formulation A, gave the maximum drug release, several additives such as 95% ethanol, polyethylene glycol 400 and DMSO were added to it at 5%, 10% and 15% concentration levels. Almost all additives except for ethanol at the 5% level adversely affected the in vitro drug release (Table 3). 

Table 2—In vitro drug release profile of microcapsules and micromatrices...

Yang, L., Chen, L., Zeng, R., Li, C, Qiao, R., Hu, L., and Li, Z. (2010). Synthesis, nanosizing and in vitro drug release of a novel anti-HIV polymeric prodrug Chitosan-O-isopropyl-50-O-d4T monophosphate conjugate. Bioorg. Med. Chem. 18,117-123. 

Shah, V. P... 1. S. Elkins, and R. L. Williams, In Vitro Drug Release Measurement of Topical Glucocorticoid Creams." Pharmacopeial Forum, 19, 5048-5059, 1993. 

Lim, S.T., et al. 2000. Preparation and evaluation of the in vitro drug release properties and mucoadhesion of novel microspheres of hyaluronic acid and chitosan. J Control Release 66 281. 

Li Wan Po, Wong, L., and Gilligan, C. Characterization of commercially available theophylline sustained- or controlled-release systems In vitro drug release profiles. Int. J. Pharm. 66 111-130, 1990. 

Figure 9.1 Effect of size on the in vitro drug release of etoposide from PLA microparticles.

In vitro drug release from transbuccal disc devices was determined at 37°C using a USP dissolution apparatus connected through a microprocessor-controlled peristaltic pump to a fraction collector. The cumulative amount released as a function of time was calculated from the drug concentration data after compensating for the total amount removed in the collected sample fractions. 

In another study, compounds 5 and 35 were incorporated in PEG/PLA nanospheres (NS) and nanocapsules (NC) [ 146]. In vitro drug release after high dilution of loaded... 

Liu C-S, Desai KGH, Meng X-H, Cheng X-G (2007) Sweet potato starch microparticles as controlled drag release carriers preaparation and in vitro drug release. Drying Technol 25 689-693... 

Yan, C., Chen, D., Gu, J., and Qin, J. (2006), Nanoparticles of 5-fluorouracil (5-FU) loaded V-succinyl-chitosan (Suc-Chi) for cancer chemotherapy Preparation, characterization—in-vitro drug release and anti-tumour activity, J. Pharm. Pharmacol., 58(9), 1177-1181. 

The physical state of the drug incorporated in a powder drug delivery system (e.g., degree of crystallinity and possible interactions with the polymer) is assessed by differential scanning calorimetry (DSC) or Fourier transform infrared (FTIR) spectroscopy. These observations can clarify the results of other parameter investigations, especially the results of in vitro drug release studies. 

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