Lipid-based systems with precipitation inhibitors as formulation approach to improve the drug bioavailability and/or lower its dose: a review

Lipid-based systems, such as self-microemulsifying systems (SMEDDS) are attracting strong attention as a formulation approach to improve the bioavailability of poorly water-soluble drugs. By applying the “spring and parachute” strategy in designing supersaturable SMEDDS, it is possible to maintain the drug in the supersaturated state long enough to allow absorption of the complete dose, thus improving the drug’s bioavailability. As such an approach allows the incorporation of larger amounts of the drug in equal or even lower volumes of SMEDDS, it also enables the production of smaller final dosage forms as well as decreased gastrointestinal irritation, being of particular importance when formulating dosage forms for children or the elderly. In this review, the technological approaches used to prolong the drug supersaturation are discussed regarding the type and concentration of polymers used in liquid and solid SMEDDS formulation. The addition of hypromellose derivatives, vinyl polymers, polyethylene glycol, polyoxyethylene, or polymetacrylate copolymers proved to be effective in inhibiting drug precipitation. Regarding the available literature, hypromellose has been the most commonly used polymeric precipitation inhibitor, added in a concentration of 5 % m/m. However, the inhibiting ability is mainly governed not only by the physicochemical properties of the polymer but also by the API, therefore the choice of optimal precipitation inhibitor is recommended to be evaluated on an individual basis

High-shear wet granulation of SMEDDS based on mesoporous carriers for Improved carvedilol solubility

Mesoporous carriers are a convenient choice for the solidification of self-microemulsifying drug delivery systems (SMEDDS) designed to improve the solubility of poorly water-soluble drugs. They are known for high liquid load capacity and the ability to maintain characteristics of dry, free-flowing powders. Therefore, five different mesoporous carriers were used for the preparation of carvedilol-loaded SMEDDS granules by wet granulation methods—in paten (manually) and using a high-shear (HS) granulator. Granules with the highest SMEDDS content (63% and 66% of total granules mass, respectively) and suitable flow properties were obtained by Syloid® 244FP and Neusilin® US2. SMEDDS loaded granules produced by HS granulation showed superior flow characteristics compared to those obtained manually. All SMEDDS granules exhibited fast in vitro release, with 93% of carvedilol releasing from Syloid® 244FP-based granules in 5 min. Upon compaction into self-microemulsifying tablets, suitable tablet hardness and very fast disintegration time were achieved, thus producing orodispersible tablets. The compaction slightly slowed down the carvedilol release ratenevertheless, upon 1 h (at pH 1.2) or 4 h (at pH 6.8) of in vitro dissolution testing, the amount of released drug was comparable with granules, confirming the suitability of orodispersible tablets for the production of the SMEDDS loaded single unit oral dosage for

A comparative study of lipid-based drug delivery systems with different microstructure for combined dermal administration of antioxidant vitamins

Antioxidant vitamins have been proven to be highly efficient in treatment of skin impaired by oxidative stress, but challenges regarding stability and skin penetration limit their therapeutic effect. Lipid-based drug delivery systems offer great potential for overcoming these drawbacks. This work aimed to identify the most promising system for combined antioxidant therapy. A comparative assessment of several systems, containing the same ingredients but differing in their microstructure, was therefore performed. Namely, microemulsions (MEs) of both types (W/O and O/W) and lyotropic liquid crystals (LLCs), simultaneously loaded with vitamin C or ascorbyl palmitate and vitamin E, were assessed. Stability, antioxidant capacity (DPPH assay), and release (Franz diffusion cells) of the vitamins incorporated was examined. The results obtained were supported with the systems’ thermal and rheological (rotational and oscillatory tests) evaluation. In addition, biological acceptability (MTS assay) of the systems studied was investigated. The findings demonstrate that the microstructure of MEs and LLCs studied has a decisive impact on the stability, antioxidant activity, and release of the vitamins incorporated. The highest stability was preserved in LLCs for both pairings, with vitamins C and E being a more stable combination. LLCs also provided suitable vitamins’ antioxidant activity and release characteristics. In addition, the system exhibited preferable rheological features for dermal administration. Furthermore, cytotoxicity studies on a keratinocyte cell line demonstrated the highest biocompatibility for LCCs with the cell proliferation being greater than 85%. In conclusion, LLCs were confirmed as the most favorable lipid-based drug delivery system for combined antioxidant treatment

The impact of phospholipid-based liquid crystals’ microstructure on stability and release profile of ascorbyl palmitate and skin performance

The drug delivery potential of liquid crystals (LCs) for ascorbyl palmitate (AP) was assessed, with the emphasis on the AP stability and release profile linked to microstructural rearrangement taking place along the dilution line being investigated by a set of complementary techniques. With high AP degradation observed after 56 days, two stabilization approaches, i.e., the addition of vitamin C or increasing AP concentration, were proposed. As a rule, LC samples with the lowest water content resulted in better AP stability (up to 52% of nondegraded AP in LC1 after 28 days) and faster API release (~18% in 8 h) as compared to the most diluted sample (29% of nondegraded AP in LC8 after 28 days, and up to 12% of AP released in 8 h). In addition, LCs exhibited a skin barrier-strengthening effect with up to 1.2-fold lower transepidermal water loss (TEWL) and 1.9-fold higher skin hydration observed in vitro on the porcine skin model. Although the latter cannot be linked to LCs’ composition or specific microstructure, the obtained insight into LCs’ microstructure contributed greatly to our understanding of AP positioning inside the system and its release profile, also influencing the overall LCs’ performance after dermal application