Biphasic gastroretentive drug delivery system of acyclovir: formulation and in vitro evaluation

A biphasic gastroretentive drug delivery system of acyclovir consisted of loading dose tablet and floating multiple matrix tablets was prepared by direct compression process. The delivery system was designed by hydroxy propyl methyl cellulose as retardant polymer with an effervescent component to get the desired buoyant and sustained release characteristics. All formulations compile within the limits. The FTIR studies did not show any evidence of an interaction between acyclovir and polymers. Dissolution studies revealed biphasic drug release pattern, with loading dose released within 30 min and floating multiple matrix tablets provided zero order sustained release profile for 12 h. It is concluded that floating multiple matrix tablets designed were particularly suitable as gastro retentive drug delivery system with anomalous non-fickian diffusion mechanism. The stability studies showed no significant change in dissolution profiles (f2 value > 50).Colegio de Farmacéuticos de la Provincia de Buenos Aire

Formulation and evaluation of multilayered matrix tablets of diltiazem hydrochloride

In the present study matrix and multilayered matrix tablets of diltiazem HCl were formulated by using guar gum as matrix core component and cellulose derivative, Sodium Carboxy Methyl Cellulose (SCMC) as barrier layers. Marked difference in dissolution characteristics of D3 and D3L3 was observed and showed a statistically significant difference. The study revealed that the matrix tablets prolonged the release, but predominantly in a first order fashion. Layering with SCMC granules on the matrix core, provided linear drug release with zero order kinetics. Mean dissolution time for D3 and D3L3 were found to be 4.17 h and 16.45 h, while dissolution efficiency decreased, indicating slower drug release. In vivo transit time of the formulation D3L3 shows that it crossed the small intestine at 6 h and retained for longer time in colon at 12 h. FT-IR and DSC studies show there is no drug-excipeints interaction. Stability studies portray that no change either in physical manifestation or in dissolution profile after storage at 40 ± 2 °C/RH 75 ± 5 % for 3 and 6 months.Colegio de Farmacéuticos de la Provincia de Buenos Aire

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

Preparation and pharmacokinetic studies of mucoadhesive oral multiple unit systems of metronidazole

The objective of the present study was to investigate the applicability of matrix type chitosan treated alginate multiple unit systems (MUS) for sustained release of metronidazole prepared by ionotropic gelation method. Spherical MUS with 0.64 ± 0.95 to 0.75 ± 0.38 mm length and 0.63 ± 0.34 to 0.74 ± 0.28 mm breadth and 71.60 ± 0.42 to 82.15 ± 0.35 % entrapment efficiency were produced. The fluoroscopic study reveals that the MUS was retained in gastrointestinal tract (GIT) for more than 5 h and found to be distributed throughout the GIT. The in vivo evaluation in healthy human volunteers of the MUS and that of Flagyl® IR tablets each containing 400 mg drug revealed that the MUS showed improved pharmacokinetic parameters to Flagyl® producing a significantly different (p < 0.05) AUC. This study demonstrates that the MUS could be a good alternative to immediate release tablets to deliver metronidazole and expected to be less irritant to gastric and intestinal mucosa.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Influence of cellulose derivatives and natural polymers on in vitro release kinetics of metoprolol succinate from extended release matrix tablets

In the present investigation, extended release tablets of metoprolol succinate were developed using cellulose derivatives and natural gums as matrix formers and were evaluated for its extended release characteristics. The optimized formulation (F7) was obtained using cellulose derivatives in the ratio of 1:0.5:1drug, HPMC K 100M and Na CMC, respectively. Prepared tablets were subjected to all the Pharmacopeial quality tests and found to be in the limits. The in vitro release studies of prepared matrix tablets with both the polymers were also studied. The kinetic treatment illustrate that the optimized formulation (F7) followed zero order kinetics with release exponent (n) 0.82 and showed good stability as per ICH guidelines. FT-IR and DSC studies indicated no chemical interaction between the drug and excipients. Oral extended release tablets of metoprolol succinate could be successfully prepared using an appropriate combination of cellulose polymers when compared with natural gumsColegio de Farmacéuticos de la Provincia de Buenos Aire

Formulation and gastrointestinal transit evaluation of mucoadhesive oral Multiple Unit Systems of Furazolidone

The objective of present study was to improve gastric residence time of furazolidone by preparing mucoadhesive Multiple Unit Systems (MUS) with chitosan, Hydroxypropyl methyl cellulose K4M and sodium carboxymethyl cellulose by employing ionotropic gelation method. The resultant MUS were evaluated in vitro and in vivo. The particle size length ranged between 0.76 ± 0.25 to 0.89 ± 0.23mm, while the breadth was 0.76 ± 0.15 to 0.89 ± 0.06 mm, respectively. Encapsulation efficiency was in range of 82 to 90 %. MUS exhibited good mucoadhesive property in in vitro wash-off test. Stability studies showed no significant change in dissolution profiles (P < 0.05). The Gastrointestinal transit time was determined by fluoroscopic study which revealed that, the MUS retained in gastrointestinal tract for more than 5 hours and distributed throughout GIT. Based upon these results, prepared mucoadhesive MUS can be a good alternative to single unit systems to deliver Furazolidone with improved gastric residence time to treat intestinal amoebiasis.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Enantiomeric separation and determination of stereospecific drug release from marketed racemic omeprazole products by chiral HPLC

The objective of carrying out this research work was to investigate the effect of chirality on stereospecific dissolution of omeprazole enantiomers from various marketed racemic omeprazole products. Omeprazole is used for the treatment of gastro-duodenal ulcers and symptomatic gastro-oesophageal reflux. Dissolution of various marketed products was performed using USP type I apparatus in 0.1 N HCl for 2 h and in pH 6.8 phosphate buffer for 1 h at 100 rpm. The separation of enantiomers was done using a chiral HPLC method on CHIRAL AGP column (100 x 4.6 mm i.d.). The wavelength for UV detection was set at 210 nm. The mobile phase was 10 mM phosphate buffer with 5 % acetonitrile adjusted to pH 6.5 at a flow rate of 0.9 ml min-1 with an injector valve fitted to a 50 μL volume sample loop. The retention times for R and S enantiomers of omeprazole were 5 and 7.5 min, respectively. The dissolution of S enantiomer of Ocid-20 and Omee was found to be significantly more compared to their R enantiomer at 5 and 10 min dissolution time points after which there was no stereospecific discrimination in the dissolution. From the S/R ratios of different racemic omeprazole marketed products it was concluded that at 5 and 10 min dissolution time points there was a stereospecific drug release between the S and R enantiomers with the brands Ocid-20 and Omee (p 0.05).Colegio de Farmacéuticos de la Provincia de Buenos Aire

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