Priprava i in vitro vrednovanje bukoadhezivnih tableta karvedilola

Buccoadhesive tablets of carvedilol were prepared using HPMC K4M, HPMC K15M and Carbopol 934 as mucoadhesive polymers. Fifteen formulations were developed with varying concentrations of polymers. Formulations of the BC or BD series were composed of HPMC K4M or HPMC K15M in ratios of 1:1 to 1:5 whereas in the BE series Carbopol 934 was used (1:0.25 to 1:1.50). The formulations were tested for in vitro drug release, in vitro bioadhesion, moisture absorption and in vitro drug permeation through porcine buccal mucosa. Formulation BC3 showed maximum release of the drug (88.7 ± 0.4%) with the Higuchi model release profile and permeated 21.5 ± 2.9% of the drug (flux 8.35 ± 0.291 µg h1cm2) permeation coefficient 1.34 ± 0.05 cm h1) through porcine buccal membrane. BC3 formulation showed 1.62 ± 0.15 N of peak detachment force and 0.24 ± 0.11 mJ of work of adhesion. FTIR results showed no evidence of interaction between the drug and polymers. XRD study revealed that the drug is in crystalline form in the polymer matrix. The results indicate that suitable bioadhesive buccal tablets with desired permeability could be prepared.Varirajući koncentracije bukoadhezivnih polimera HPMC K4M, HPMC K15M i Carbopol 934 pripravljeno je 15 tableta karvedilola. Pripravci iz serije BC ili BD izrađeni su iz karvedilola i HPMC K4 M ili HPMC K 15M u omjerima 1:1, 1:2, 1:3, 1:4 i 1:5, a pripravci iz BE serije iz karvedilola i Carbopol 934 u omjerima 1:0.25, 1:0.50, 1:0.75, 1:1.00 i 1:1.50. In vitro je ispitivana brzina oslobađanja ljekovite tvari, bioadhezija, apsorpcija vlage i permeacija kroz bukalnu membranu svinje. Iz pripravka BC3 postignuto je maksimalno oslobađanje (88,7 + 0,4 %) koje je slijedilo Higuchijev model i maksimalna permeacija 21,5 + 2,9 % (fluks 8,35 ± 0,291 µg h-1 cm-2; permeacijski koeficijent 1,34 ± 0,05 cm h-1). Sila odvajanja za taj pripravak bila je 1,62 ± 0,15 N, a adhezija 0,24 ± 0,11 mJ. FTIR ispitivanja su pokazala da nije bilo interakcija između ljekovite tvari i polimera, a XRD ispitivanja da je ljekovita tvar u kristaliničnoj formi u polimernom matriksu. Pripravljene bukalne tablete su dovoljno bioadhezivne, a permeacija iz njih je zadovoljavajuća

FORMULATION AND IN VIVO EVALUATION OF SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM OF RAMIPRIL IN WISTAR RATS

Objective: The aim was to formulate and evaluate self-nanoemulsifying drug delivery systems (SNEDDS) of ramipril, an antihypertensive drug to improve the solubility and bioavailability. Methods: Based on solubility studies oil phase (Sefsol 218), surfactant (Acrysol EL135), and cosurfactant (Transcutol P), respectively, were selected to prepare SNEDDS. Ramipril SNEDDS optimized employing box-Behnken design through the study of factors. All formulations were evaluated for particle size, zeta potential (ZP), polydispersity index (PDI), entrapment efficiency (EE), drug content, and in vitro drug release. The optimized formulation was characterized for Fourier transform infrared (FTIR), scanning electron microscopy (SEM), stability studies, and pharmacokinetic study. Results: The mean particle size, PDI, ZP, EE, content uniformity, and in vitro drug release profile of optimized ramipril-loaded SNEDDS (RF14) were found to be 75.3±2.21nm, 0.126±0.05, −24.4±5.78mV, 98.74±1.97%, 99.52±1.67%, and 98.65±1.73%, respectively. FTIR studies revealed that there is no incompatibility between drug and excipients, SEM images exhibited nanoparticles to be more porous and in spherical shape. Stability studies indicated formulation was stable for 6 months. In vivo studies were conducted for optimized formulation RF14, the Tmax was found to be 0.5±0.62 and 0.5±0.95 h for the optimized and commercial formulations respectively, while Cmax was 25.16±1.73 ng/mL was significant (p<0.05) as compared to the ramipril pure drug 8.02±0.086 ng/mL. AUC0-t of the SNEDDS formulation was higher 355.49±1.76ng h/ml compared to pure drug 116.57±1.64 ng h/ml indicated higher amount of drug concentration in blood proving better systemic absorption of ramipril from SNEDDS formulation as compared to the pure drug. Conclusion: It is concluded from the results that ramipril was successfully formulated into SNEDDS with higher concentration with fast action