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

Priprava i evaluacija dvofazičnih plutajućih tableta fenoverina

A biphasic gastroretentive drug delivery system of fenoverine was developed to maintain constant plasma concentration. The delivery system consisted of a loading-dose tablet and a floating multiple matrix tablet prepared by the direct compression process. The drug release from biphasic GRDDS in 0.1 mol L1 HCl and SGF (enzyme free) was sustained over 12 h with buoyant properties. Stability studies showed no significant change in dissolution profiles (f2 value > 50). Based on the release kinetics, it can be concluded that the floating multiple matrix tablet containing HPMC was a particularly suitable gastroretentive drug delivery system with a zero-order release profile.U radu je opisan razvoj bifazičnog sustava za isporuku fenoverina s produljenim zadržavanjem u želucu radi održavanja konstantne koncentracije lijeka u plazmi. Sustav je dobiven metodom izravne kompresije, a sastoji se od tablete za inicijalno doziranje i matriksne tablete za plutanje. Oslobađanje lijeka iz bifazičnog GRDDS u 0,1 mol L1 HCl i SGF (bez enzima) bilo je produljeno više od 12 h, a sustav je pokazao plutajuća svojstva. Ispitivanja stabilnosti pokazala su da nema značajne promjene u profilu oslobađanja (f2 > 50). Na temelju kinetike oslobađanja može se zaključiti da su plutajuće višeslojne matriksne tablete s HPMC posebno pogodan sustav za isporuku fenoverina u želucu s kinetikom oslobađanja nultog reda

Lipid nanoparticles for transdermal delivery of flurbiprofen: formulation, in vitro, ex vivo and in vivo studies

The aim of the study is to prepare aqueous dispersions of lipid nanoparticles – flurbiprofen solid lipid nanoparticles (FLUSLN) and flurbiprofen nanostructured lipid carriers (FLUNLC) by hot homogenization followed by sonication technique and then incorporated into the freshly prepared hydrogels for transdermal delivery. They are characterized for particle size, for all the formulations, more than 50% of the particles were below 300 nm after 90 days of storage at RT. DSC analyses were performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by TEM which revealed fairly spherical shape of the formulations. Further they were evaluated for in vitro drug release characteristics, rheological behaviour, pharmacokinetic and pharmacodynamic studies. The pharmacokinetics of flurbiprofen in rats following application of SLN gel (A1) and NLC gel (B1) for 24 h were evaluated. The Cmax of the B1 formulation was 38.67 ± 2.77 μg/ml, which was significantly higher than the A1 formulation (Cmax = 21.79 ± 2.96 μg/ml). The Cmax and AUC of the B1 formulation were 1.8 and 2.5 times higher than the A1 gel formulation respectively. The bioavailability of flurbiprofen with reference to oral administration was found to increase by 4.4 times when gel formulations were applied. Anti-inflammatory effect in the Carrageenan-induced paw edema in rat was significantly higher for B1 and A1 formulation than the orally administered flurbiprofen. Both the SLN and NLC dispersions and gels enriched with SLN and NLC possessed a sustained drug release over period of 24 h but the sustained effect was more pronounced with the SLN and NLC ge

Optimization, Characterisation and Pharmacokinetic Studies of Mucoadhesive Oral Multiple Unit Systems of Ornidazole

The objective of the present study was to investigate the applicability of matrix type mucoadhesive oral multiple unit systems (MUS) for sustaining the release of ornidazole in the gastrointestinal tract (GIT). The MUS were prepared by ionotropic gelation method using chitosan and hydroxypropyl methyl cellulose K4M (HPMC K4M) according to 32 factorial designs and were evaluated in vitro and in vivo. The particle size length ranged from 0.78 to 1.30 mm and breadth from 0.76 to 1.30 mm, respectively. The entrapment efficiency was in range of 80 to 96%. The rapid wash-off test was observed faster at intestinal pH 6.8 as compared to acidic pH 1.2. The fluoroscopic study revealed the retention of MUS in GIT for more than 5 hours. The pharmacokinetic parameters Cmax, Tmax, mean residence time (MRT) and area under curve (AUC) of developed MUS were found to be improved significantly (p<0.05) when compared with marketed immediate release tablets each containing 500 mg of drug. This study demonstrates that the MUS could be a good alternative to immediate release tablets to deliver ornidazole and expected to be less irritant to gastric and intestinal mucosa

Effect of Ashwagandha and Aloe vera pretreatment on intestinal transport of buspirone across rat intestine

The transport of buspirone across rat intestine (duodenum, jejunum, ileum and colon) was studied by using the non-everted sac method. Rats were pretreated with ashwagandha (Withania somnifera) and Aloe vera juice for 7 days. The rats were sacrificed by using anesthetic ether, the intestinal segments were isolated and used for the studies. The probe drug (buspirone) solution was placed in the isolated intestinal sac. Samples were collected at preset time points and replaced with fresh buffer. The drug content in the samples was estimated using high performance liquid chromatography method. Control experiments were also performed. The results reveal that there was a significant (p < 0.05) difference compared to control, in the transport of buspirone from the intestinal sacs which were pretreated with ashwagandha and Aloe vera juice. It suggests that both ashwagandha and Aloe vera might be acting by inhibiting the transporters and enzymes which are responsible for transport/metabolism of buspirone.Colegio de Farmacéuticos de la Provincia de Buenos Aire

DESIGN AND IN VIVO EVALUATION OF METOPROLOL TARTRATE BILAYER FLOATING TABLETS IN HEALTHY HUMAN VOLUNTEERS

The aim of the present investigation was to prepare bilayer floating tablets of metoprolol tartrate using the combination of superdisintigrants, HPMC K grade polymers and natural polymers like xanthan gum and guar gum by direct compression method. Bilayer floating tablets were prepared using optimized immediate release layer and floating layer as sustained release layer. The physico-chemical characteristics of the prepared tablets were evaluated and found to be satisfactory. All the prepared batches showed in vitro buoyancy. It was observed that the tablets remained buoyant for more than 12 h.  Formulation F7 was selected as best formulation based on the in vitro characteristics and used in vivo radiographic studies by adding barium sulphate. These studies revealed that the tablets remained in the stomach for 210±5.4 min (n=3) in fasting human volunteers. Based on the in vivo performance in healthy subjects, the developed bilayer floating tablets showed superior bioavailability than the marketed tablets, the drug release was up to 12 h in controlled manner. The systemic availability of the best formulation was high after administration to obtain immediate action due to the immediate release layer, from sustained release layer the drug was released in controlled manner. It can be concluded that the best formulation F7 by choosing biphasic drug release pattern in a single dosage form could improve patient compliance and ensure better disease management

DESIGN AND IN VIVO EVALUATION OF METOPROLOL TARTRATE BILAYER FLOATING TABLETS IN HEALTHY HUMAN VOLUNTEERS

The aim of the present investigation was to prepare bilayer floating tablets of metoprolol tartrate using the combination of superdisintigrants, HPMC K grade polymers and natural polymers like xanthan gum and guar gum by direct compression method. Bilayer floating tablets were prepared using optimized immediate release layer and floating layer as sustained release layer. The physico-chemical characteristics of the prepared tablets were evaluated and found to be satisfactory. All the prepared batches showed in vitro buoyancy. It was observed that the tablets remained buoyant for more than 12 h.  Formulation F7 was selected as best formulation based on the in vitro characteristics and used in vivo radiographic studies by adding barium sulphate. These studies revealed that the tablets remained in the stomach for 210±5.4 min (n=3) in fasting human volunteers. Based on the in vivo performance in healthy subjects, the developed bilayer floating tablets showed superior bioavailability than the marketed tablets, the drug release was up to 12 h in controlled manner. The systemic availability of the best formulation was high after administration to obtain immediate action due to the immediate release layer, from sustained release layer the drug was released in controlled manner. It can be concluded that the best formulation F7 by choosing biphasic drug release pattern in a single dosage form could improve patient compliance and ensure better disease management

Stereospecific dissolution of inclusion complexes of amlodipine base and its besylate enantiomers with hydroxypropyl-β-cyclodextrin

The objective of this work was the preparation of inclusion complexes of amlodipine base and its besylate salt with hydroxy propyl-β-cyclodextrin (HPBC) to improve the dissolution and to investigate the stereospecific dissolution of amlodipine enantiomers. The prepared inclusion complexes were characterized by FTIR and DSC. Significant improvement in the dissolution was found with S and R enantiomers of amlodipine base where as no improvement was found with enantiomers of amlodipine besylate (p > 0.05) after complexation with HPBC. This indicates the formation of inclusion complexes with only enantiomers of amlodipine base (p 0.05). Stereospecific dissolution was observed with pure enantiomers of amlodipine base when its inclusion complexes were prepared by solvent evaporation method with l:1 and 1:2 molar ratios but not with 1:3 molar ratio.Colegio de Farmacéuticos de la Provincia de Buenos Aire

DEVELOPMENT AND IN-VITRO EVALUATION OF NICOTINE TROCHES FOR SMOKING CESSATION

Objective: Nicotine replacement therapy is a way of getting nicotine into bloodstream without smoking. The present investigation aims to design, prepare and evaluate compressed tablet lozenges or troches of nicotine 2mg for low dependent smokers and, 4mg for high dependent smokers, sugar free troches. The benefits of these prepared lozenges are increased bioavailability, reduction in gastric irritation by reducing first pass metabolism.Method: The lozenges were prepared by wet granulation method.Results and discussion: All the formulations prepared were subjected to various physico-chemical parameters like hardness, content uniformity, friability, weight variation etc.The prepared formulations have a hardness of 9-12 Kg. /cm². Sugar free troches with kyron T 114 (1:4 molar ratio) for 2mg and (1:6 molar ratio) for 4mg showed decreased burning after taste and pungent odor and provided good taste. Stability study of selected formulations was also carried out at 37ºC for a period of six months. Selected formulations were tested for drug excipient interactions subjecting to FTIR Spectral analysis. In-vitro drug dissolution studies showed 100% for optimized formulations.Conclusions: Sugar free troches are useful for diabetic smokers. Troches can provide an attractive alternative formulation in the Nicotine replacement therapy. Key words: Nicotine; Troches; Lozenges; Hydroxyl Propyl Methyl Cellulos