Influence of Solid Drug Delivery System Formulation on Poorly Water-Soluble Drug Dissolution and Permeability

Abstract

Abstract:The majority of drugs have a low dissolution rate, which is a limiting step for their absorption. In this manuscript, solid dispersions (SD), solid self-microemulsifying drug delivery systems (S-SMEDDS) and solid self-nanoemulsifying drug delivery systems (S-SNEDDS) were evaluated as potential formulation strategies to increase the dissolution rate of carbamazepine. Influence of increased dissolution rate on permeability of carbamazepine was evaluated using PAMPA test. In S-SMEDDS and S-SNEDDS formulations, the ratio of liquid SMEDDS/SNEDDS and solid carrier (Neusilin ® UFL2) was varied, and carbamazepine content was constant. In SD formulations, the ratio of carbamazepine and Neusilin ® UFL2, was varied. Formulations that showed the best dissolution rate of carbamazepine (SD_1:6, SMEDDS_1:1, SNEDDS_1:6) were mutually compared, characterization of these formulations was performed by DSC, PXRD and FT-IR analyses, and a PAMPA test was done. All formulations have shown a significant increase in dissolution rate compared to pure carbamazepine and immediate-release carbamazepine tablets. Formulation S-SMEDDS_1:1 showed the fastest release rate and permeability of carbamazepine. DSC, PXRD and FT-IR analyses confirmed that in S-SMEDDS and S-SNEDDS carbamazepine remained in polymorph form III, and that it was converted to an amorphous state in SD formulations. All formulations showed increased permeability of carbamazepine, compared to pure carbamazepine.

Effect of Cyclodextrin Types and Co-Solvent on Solubility of a Poorly Water Soluble Drug

“…Various methods, for example, salt formation, co-solvency, micellar solubilization, solid dispersions and complexation by cyclodextrins (CDs), nanosizing and particles engineering have been used successfully to increase the solubility of drugs [1,2,3,4]. Recently, lipid drug delivery systems or nano-emulsions have been investigated, especially for highly lipophilic drugs [5,6]. Although these conventional solubilization techniques have been well-described and used successfully for many drugs, each possesses limitations in terms of the solubilizing capacity, patient acceptability and safety [7,8].…”

Solid dispersions with carbamazepine: Optimization of formulation, characterization and examination of long-term stability

“…Simulacija bioloških membrana postiže se odgovarajućim odabirom rastvarača i supstanci od kojih se formira veštačka membrana. Dugi niz godinа se PAMPA test koristio u proceni permeаbilnosti novosintetisаnih lekovitih susptаnci, а tek poslednjih godinа se koristi za ispitivаnje permeаbilnosti lekovite supstаnce iz rаzličitih fаrmаceutskih oblikа i sаvremenih nosаčа [8,9,12,13].…”

In vitro screening of nanomedicines through the blood brain barrier: A critical review

“…However, the PAMPA assay has found so far greater acceptance for gastrointestinal tract passive transport prediction, since a broader spectrum of nanomedicines has already been tested, such as polymeric micelles [128], [129,130], liposomes [131,132], solid lipid nanoparticles [133] and solid self-nanoemulsifying drug delivery systems [134,135]. Overall, results pointed out that inclusion in nanocarriers may significantly alter the passive diffusion pattern of the free drug.…”