Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique

Abstract

The objective of this work was to prepare an oil/water glimepiride (GM) microemulsion (ME) for oral administration to improve its solubility and enhance its bioavailability. Based on a solubility study, pseudoternary phase diagrams, and Box–Behnken design, the oil/water GMME formulation was optimized and prepared. GMME was characterized by dynamic laser light scattering, zeta potential, transmission electron microscopy, and viscosity. The in vitro drug release, storage stability, pharmacodynamics, and pharmacokinetics of GMME were investigated. The optimized GMME was composed of Capryol 90 (oil), Cremophor RH40 (surfactant), and Transcutol (cosurfactant), and increased GM solubility up to 544.6±4.91 µg/mL. The GMME was spherical in shape. The particle size and its polydispersity index were 38.9±17.46 nm and 0.266±0.057, respectively. Meanwhile, the GMME was physicochemically stable at 4°C for at least 3 months. The short-term efficacy in diabetic mice provided the proof that blood glucose had a consistent and significant reduction at a dose of 375 µg/kg whether via IP injection or IG administration of GMME. Compared with the glimepiride suspensions or glimepiride-meglumine complex solution, the pharmacokinetics of GMME in Wistar rats via IG administration exhibited higher plasma drug concentration, larger area under the curve, and more enhanced oral bioavailability. There was a good correlation of GMME between the in vitro release values and the in vivo oral absorption. ME could be an effective oral drug delivery system to improve bioavailability of GM.

Development of Multi-Compartment 3D-Printed Tablets Loaded with Self-Nanoemulsified Formulations of Various Drugs: A New Strategy for Personalized Medicine

“…Administration of RSV as an oral tablet loaded with a SNEDDS formulation leads to enhancement in the drug dissolution and absorption which was reflected on its bioavailability. GLMP is characterized by its low aqueous solubility (1.6 µg/mL) and slow dissolution rate, an effect that leads to low and variable oral drug bioavailability [ 47 , 48 ]. Enhancement in GLMP dissolution is expected to have a positive impact on the drug relative bioavailability from the developed 3DP tablets.…”

Evaluation of Micro and Nanoemulsions in Pharmaceutical Aspect

“…Fakat üstesinden gelinmesi gereken kinetik enerji bariyerleri veya spontan oluşumunu geciktiren sınırlamalar olduğu için, mikroemülsiyon oluşumunu kolaylaştırmak için genellikle karıştırma veya ısıtma şeklinde bir dış enerji uygulamak gereklidir. 3,9 Nanoemülsiyon formülasyonunda içerik sıralaması çok önemlidir ve nanoemülsiyonlar yalnızca yüzey etken maddelerin yağ fazı ile karıştırılmasıyla oluşur. Yağ fazı eklenmeden önce su ile karıştırma yapıldığında, yalnızca bir "makroskobik" emülsiyon oluşur, ayrıca termodinamik açıdan kararsız sistemler olan nanoemülsiyonlara her zaman harici enerji uygulanması gerekir.…”

“…GM süspansiyonları veya GM-meglumin kompleks çözeltisi ile karşılaştırıldığında, GM veriminin IG verimi yoluyla Wistar sıçanlarındaki farmakokinetiği, daha yüksek plazma ilaç derişimi, eğri altında daha geniş alan ve daha gelişmiş oral biyoyararlanım sergilediği gözlenmiştir. 3 Jain ve ark. ise etopozidin parenteral uygulanması için fosfolipit bazlı mikroemülsiyon formülasyonunu geliştirmişlerdir.…”

“…Ancak, ilaç piyasası göz önüne alındığında, diğer ilaç şekillerine oranla daha az sayıda emülsiyon dozaj şekillerinin mevcut olmasının en önemli gerekçesinin, emülsiyonların stabilite sorunları ile ilgili olduğu belirtilmektedir. 3 Geleneksel emülsiyonların yanı sıra, son yıllarda "mikro ve nanoemülsiyon" olmak üzere 2 yeni emülsiyon kavramı daha ortaya çıkmıştır. Mikroemülsiyonlar; berrak, termodinamik olarak kararlı, izotropik sıvı karışımlardır.…”

Development and characterization of self-nanoemulsifying drug delivery system (SNEDDS) formulation for enhancing dissolution of fenofibric acid

“…Several techniques which can be used to improve solubility and dissolution of drugs include lipid-based formulations, such as liposomes [5,6], solid lipid nanoparticles [7,8], nanostructured lipid carriers [9,10], micro/nanoemulsion [11,12], and self-nanoemulsifying drug delivery systems (SNEDDS) [13][14][15][16][17][18][19]. Lipid-based formulation increases the absorption of a poorly water-soluble drug from the gastrointestinal tract by 1) increasing drug solubilization (accelerate the dissolution process) 2) by recruiting intestinal lymphatic drug transport (reduced first-pass metabolism), and 3) by interacting with enterocytes-based transport processes [20].…”