Statistical optimization of floating-bioadhesive drug delivery system for risedronate sodium: In vitro, ex vivo and in vivo evaluation

AbstractThe objective of the present investigation was to apply statistical design for the development of risedronate sodium floating-bioadhesive tablets (RSFBT) employing response surface methodology (RSM). A central composite design (CCD) was developed using Design of Expert (DOE) software to study the effect of formulation variables on the drug delivery system. The RSFBT were prepared by direct compression using hydroxy propyl methyl cellulose (HPMC K100M) as release retardant; carbopol (CP 974P) as bioadhesive polymer and sodium bicarbonate (NaHCO3) as a gas-former. The quantities of HPMC K100M (X1), CP 974P (X2) and NaHCO3 (X3) were taken as independent variables and percentage drug release at 2 h (Q2), 6 h (Q6) and 12 h (Q12), floating lag time (FLT), total floating time (TFT) and bioadhesive strength (BS) were selected as responses. The BS was determined using porcine gastric mucosa. In all 15 formulations were prepared and studied. The results of the CCD indicated that high levels of both X1 and X3, and low level of X2 were required for the preparation of RSFBT. Further, a good correlation was observed between predicted and experimental values of the independent variables selected for this study. The drug release profiles of all the formulations were fitted into zero-order, first-order, Higuchi and Peppas models. The optimized formulation followed the Peppas model with a non-Fickian diffusion mechanism. The statistically optimized formulation (RSFBTsopt) was found to be physically stable when stored at 40 ± 2 oC/75 ± 5% RH for 3 months. In vivo evaluation of RSFBTsopt, BaSO4-loaded tablets revealed a mean gastric retention time of 5 ± 0.86 h (n=3) in healthy volunteers.

Development, intra-gastric performance and pharmacokinetic study of gastroretentive drug delivery system for cefdinir in human volunteers

The objective of this study was to develop sustained-release floating tablets of cefdinir (CFDN) using effervescent technique to prolong gastric residence time (GRT) and compare their pharmacokinetics with immediate release (IR) and conventional sustained release (SR) tablets. The tablets were designed using CaCO3 as gas-former and three grades of polyethylene oxide as release-retardants and further were evaluated for their physical characters, in vitro drug release and buoyancy studies. The optimized formulation (F3) was found to be physically stable when stored at 40 oC/75% RH for 3 months. In vivo radiographic imaging of F3 revealed a mean GRT of 4.83 ± 0.57 h (n=3). Comparative pharmacokinetic study was performed for F3, IR and SR tablets of CFDN in humans. Based on in vivo performance, the difference between tmax, AUC0-∞, t1/2 and MRT of F3, IR and SR tablets were found to be statistically significant (p < 0.05). The difference between Cmax of F3 and IR tablet was statistically significant, but the Cmax of F3 and SR tablet was not statistically significant. The relative bioavailability of F3 was 1.71 fold to IR and 1.24 fold to SR. This improved bioavailability is due to the combined effect of sustained release and increased GRT

Development, intra-gastric performance and pharmacokinetic study of gastroretentive drug delivery system for cefdinir in human volunteers

The objective of this study was to develop sustained-release floating tablets of cefdinir (CFDN) using effervescent technique to prolong gastric residence time (GRT) and compare their pharmacokinetics with immediate release (IR) and conventional sustained release (SR) tablets. The tablets were designed using CaCO3 as gas-former and three grades of polyethylene oxide as release-retardants and further were evaluated for their physical characters, in vitro drug release and buoyancy studies. The optimized formulation (F3) was found to be physically stable when stored at 40 oC/75% RH for 3 months. In vivo radiographic imaging of F3 revealed a mean GRT of 4.83 ± 0.57 h (n=3). Comparative pharmacokinetic study was performed for F3, IR and SR tablets of CFDN in humans. Based on in vivo performance, the difference between tmax, AUC0-∞, t1/2 and MRT of F3, IR and SR tablets were found to be statistically significant (p < 0.05). The difference between Cmax of F3 and IR tablet was statistically significant, but the Cmax of F3 and SR tablet was not statistically significant. The relative bioavailability of F3 was 1.71 fold to IR and 1.24 fold to SR. This improved bioavailability is due to the combined effect of sustained release and increased GRT

Razvoj i vrednovanje plutajućih tableta norfloksacina s produljenim zadržavanjem u želucu

Floating matrix tablets of norfloxacin were developed to prolong gastric residence time, leading to an increase in drug bioavailability. Tablets were prepared by the wet granulation technique, using polymers such as hydroxy propyl methylcellulose (HPMCK4M, HPMCK100M) and xanthan gum. Tablets were evaluated for their physical characteristics viz., hardness, thickness, friability, and mass variation, drug content and floating properties. Further, tablets were studied for in vitro drug release characteristics for 9 hours. The tablets exhibited controlled and prolonged drug release profiles while floating over the dissolution medium. Non-Fickian diffusion was confirmed as the drug release mechanism from these tablets, indicating that water diffusion and the polymer rearrangement played an essential role in drug release. The best formulation (F4) was selected based on in vitro characteristics and was used in vivo radiographic studies by incorporating BaSO4. These studies revealed that the tablets remained in the stomach for 180 ± 30 min in fasting human volunteers and indicated that gastric retention time was increased by the floating principle, which was considered desirable for absorption window drugs.Razvijene su plutajuće tablete norfloksacina koje se produljeno zadržavaju u želucu i time povećavaju bioraspoloživost. Tablete su pripravljene metodom vlažne granulacije, koristeći hidroksipropil metilcelulozu (HPMCK4M, HPMCK100M) i ksantan gumu. Tabletama su određena fizikalna svojstva (čvrstoća, debljina, lomljivost i varijacija mase) te sadržaj ljekovite tvari i plutajuća svojstva. Nadalje, praćeno je oslobađanje ljekovite tvari in vitro tijekom 9 h. Uočeno je da je oslobađanje kontrolirano i produljeno te da tablete plutaju u ispitivanom mediju. Mehanizam oslobađanja nije slijedio Fickov zakon, što ukazuje da difuzija vode i promjene u strukturi polimera imaju bitnu ulogu u oslobađanju ljekovite tvari. Najbolja formulacija (F4) in vitro uporabljena je s dodatkom barijevog sulfata za radiografska ispitivanja in vivo. Ispitivanja na volonterima koji su apstinirali od hrane pokazala su da primjena plutajućih tableta produljuje vrijeme zadržavanja u želucu na 180 ± 30 min