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.
Highlights
Oral administration of drugs is considered to be the most natural, uncomplicated, convenient and safe method
It can be concluded that upon high water dilution, Self-microemulsifying drug delivery systems (SMEDDS) is capable of forming oil-in-water microemulsions, because the droplet size is less than 100 nm
SMEDDS had monomodal droplet size distribution with a polydispersity index (PDI) value of 0.104 ± 0.005 and droplet size of (17.66 ± 0.17 nm), which indicates that a stable microemulsion was formed
Summary
Oral administration of drugs is considered to be the most natural, uncomplicated, convenient and safe method. Since nearly one third of drugs are poorly water soluble, oral bioavailability of those drugs could be an issue [1]. Carbamazepine is an antiepileptic agent with low solubility (0.15 ± 0.07 mg/mL, 25 °C, [2]) and high permeability, which makes it a great candidate for this study. Classification System (BCS) that classifies drugs into four categories according to their permeability and solubility properties, carbamazepine is classified as a class II drug. As dissolution of poorly water-soluble drugs (e.g., carbamazepine) is the rate-limiting step for absorption, improvement of dissolution rate should increase drug absorption and bioavailability [3,4]. Carbamazepine is susceptible to polymorphic transition, so it is a great candidate in the evaluation of the influence of excipients on polymorphic form
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