The aim of present study was to formulate & evaluate the mucoadhesivesustainedrelease formulations of lamivudine. And to fulfil this aim, two mucoadhesive formulations- gels and tablets were prepared by using three different polymers: HPMC K15, poloxamer 407 & carbopol 934. Three mucoadhesive gel and nine tablet formulations were prepared and evaluated for various parameters. All prepared gel & tablet formulations had good physico-mechanical properties. Among all the formulations, carbopol gel and tablets showed the highest mucoadhesive force, although, each formulation had good adhesive force. All three gels were able to give sustainedrelease up to 12 hours. Tablet formulations, so from this study, it is concluded that mucoadhesive formulations of lamivudine can be prepared for sustaining its release. And the successful outcome of the present study also encourage for further studies to assess the ability of the mucoadhesive formulations of lamivudine in providing an effective sustained and safe therapy for AIDS.
The ex vivo mucoadhesion time studies were performed after application of tablet and patch, respectively, on freshly cut goat stomach mucosa. The mucosa was fixed on a glass slide using double-sided adhesive, and one side of glass slide was fixed to thread whose another end was fixed with the arm of tablet disintegration test apparatus. A side of each tablet and patch was wetted with dissolution medium and was attached to the mucosa by applying a light force with a fingertip for 20 s. The beaker was filled with 800 mL of phosphate buffer of pH 6.8 maintained at 37±0.50°C were used as disintegration medium and after 2 min the slide was placed in a beaker, and the apparatus was started. Care was taken that while up and down motion of the arm tablet and patch should remain in the medium. Behavior and mucoadhesive time of tablet and patch were monitored until complete detachment occurred . Folding endurance
The aim of the present investigation was to develop sustainedrelease matrix tablets containing methimazole. The different batches were manufactured by direct compression method using hydrophilic swellable carbopol and ethocel and eudragit RL100 in combination using Minipress and characterized by FTIR, DSC, in vitro mucoadhesion, in vitro swelling, erosion and in vitro drug release and stability studies. It was found that, the formulation batch MT 6 has a mucoadhesion force about 14.813 ± 0.085 N. It has exhibited the adhesion retention time about 11.16 ± 0.10 h in the entire region of GIT with maximum swelling up to 59.52 ± 4.93 %. It is revealed that drug release by both mechanism diffusion and erosion. Carbopol 934P along with Eudragit RL100 and ethyl cellulose was found to be controlling the release rate of methimazole in matrix tablets for 20 h. It can be concluded that, there is promising potential for this system that can control the release up to 20 h and extend the drug release. Key words: Carbopol 934P, Eudragit RL100, Ethyl cellulose, Methimazole, Matrix tablet, Percent swelling, Sustain release.
The aim of proposed research work is to isolate the natural mucoadhesive polymer from natural source (Date Palm) & formulation and evaluation of gastro mucoadhesiveSustainedrelease matrix tablet. The maximum utilisation of Mucoadhesive drug delivery system of drug which enables reduction in total amount of dose administered in fluctuation and therefore better control of diseased condition. Mucoadhesive drug delivery system of repaglinide is indicated only for type 2 Diabetes Mellitus. It should be avoided in liver disease. The aim is to drug residence time in stomach by development and evaluation of In vitro performances of gastro mucoadhesivesustainedrelease (GMSR) of Repaglinide. Gastro mucoadhesivesustainedrelease formulations (GMSR) of Repaglinide were developed by the direct compression method and these were measured by ‘modified balance method’.
that they permit adequate wetting by the mucus and optimal fluidity that permits the mutual absorption and interpenetration of polymer and mucus. The effective study was made to formulate the mucoadhesive tablets of pantoprazole sodium sesquihydrate as a model drug whose half-life is 1hour. Mucoadhesivesustainedrelease systems increase the effectiveness of drug by maintaining the drug concentration in therapeutic level and permitting targeting and localization of medication at specific site. The period of contact and intimacy between polymer-drug particles and tissue layer surface is accrued by mucoadhesion. The pantoprazole could be a proton pump inhibitor, belongs to group of benzimidazole, used for the treatment of gastric and duodenal ulcers 2, 3 . In this research work
The sustainedrelease of amoxicillin could be formulated in various forms, e.g. microspheres, beads and microcapsules, floating tablets. Ethyl cellulose (EC), a hydrophobic polymer which is non-toxic and inert, is used in most of the controlled release formulations as a mucoadhesive polymer for sustaining the drug release. Instead of formulating amoxicillin mucoadhesivesustained-release tablets by the normal trial method, a statistical experimental design i.e. Design of Experiments (DoE) was used which involves selection of independent and dependent variables. These concentrations of independent variables were selected by referring hand book of pharmaceutical excipients, literature search and experimentation done by other authors. Mucoadhesive polymers like Hydroxy Propyl Methyl Cellulose K15, Chitosan and Ethyl Cellulose were selected as independent variables to increase the residence time of amoxicillin in the stomach and ex-vivo mucoadhesion time and drug release at 24 h and t 50 % were selected as dependent variables/factors. 10
Over the past 38 years, as the expense and complications involved in marketing new drug entities have increased, with concomitant recognition of the therapeutic advantages of novel drug delivery, greater attention has been focused on development of a modified release drug delivery systems. A mucoadhesive controlled release device can improve the effectiveness of drug by helping to maintain a drug concentration between the effective and toxic level, inhibiting the dilution of drug in the body fluid and allowing targeting and localizing of a drug at a specific site. The objective of the present study is to formulate the mucoadhesive Bilayer tablets of Metformin Hydrochloride and Glyburide .The mucoadhesivesustainedrelease layer was formulated with Metformin Hydhochoide, along with Na-CMC and HPMC in combination as mucoadhesive polymers with ethyl cellulose as insoluble polymer to maintain the integrity of tablets. The immediate release layer was formulated with Sodium Starch Glycolate as super disintegrants. The bilayer tablets were formulated using wet granulation technique for mucoadhesive layer and direct compression for immediate release layer. All the physicochemical properties of the tablets were evaluated. The exvivo technique use to study the mucoadhesive strength and duration of the tablets against bovine intestine. From the study it found that the Formulation F2 with Na-CMC: HPMC in ratio 4:1 in mucoadhesive layer shows release of 89.17% of Metformin Hydrochloride in 12 hrs and 4% Sodium starch glycolate shows maximum release of 98.07% of Glyburide in first 10 minutes. The drug release follows the Higuchi release model and n value showed anomalous release profile. The swelling index increases with increase in the concentration of anionic polymers and its combination with non-ionic polymers. Increase in the swelling index leads to increase in mucoadhesion of the tablets. The mucoadhesion strength was found to be maximum for F2 formulation (0.287 N) and the tablet adhere to the membrane for more than 10 hrs. Effective mucoadhesive bilayer tablets were formulated using HPMC, Na CMC to deliver the drug for more than 10 hrs at the targeted site.
It has been observed that the first three mucoadhesive vaginal formulations, i.e., F-I, F- II and F-III, were prepared by mixing of a single polymer (Carbopol) in various ratios as a disintegrating agent, and Sodium Starch Glycolate for developing mucoadhesive action with the active drug ingredient. The best outcomes were observed in case of F-III having average weight 563.2 ± 13.95 mg, thickness 3.42 ± 0.02 mm, hardness 1.8 ± 7.51 kg/sq.cm, friability 1.04% w/w, surface pH 3.40 ± 0.11, swelling Index at 24 h 131.00 ± 2.63% w/w and mucoadhesive force of 0.137 ± 0.03 Newton. After three trials of each of these 3 formulations, they were not considered feasible due to quick disintegration, less pH value, more swelling index, and less mucoadhesive tension. The next set of formulations, F-IV to F-VI, were prepared as standard mucoadhesivesustainedrelease herbal vaginal drug delivery system in the form of tablets by mixing of the same concentration of active ingredient of research drug (500 mg) with various ratios of the polymers such as Hydroxy- Propyl-Methyl Cellulose (HPMC K4 M) to get sustainedrelease property along with a binder (maize starch), sodium starch Glycolate (SSG), diluent (Lactose monohydrate) and glidant (Talc) to increase total weight of tablets up to 700 mg. Only in the case of F-VI, Gum acacia was added to increase its binding properties.
The aim of present study was to formulate & evaluate the mucoadhesivesustainedrelease formulations of lamivudine and to fulfill this aim, two mucoadhesive formulations Gels and Tablets were prepared by using three different polymers: HPMC K15, poloxamer 407 & carbopol 934. Three mucoadhesive gel and nine tablet formulations were prepared and evaluated for various parameters. All three gels were able to give sustainedrelease up to 12 hours. Tablet formulations, F1 to F5 failed to fulfill the aim. Only F6, F7, F8 & F9 formulations were selected, as all gave sustainedrelease up to 12 hours, except F6, which gave sustainedrelease profile only till 7 hours. From the drug release plots, it was concluded that the type of polymer and concentration of polymer have distinct effect on in vitro drug release profile and all the formulations follow first order mechanism with anomalous diffusion or non-fickian diffusion, except carbopol gel and poloxamer tablets. Carbopol gel follows zero order release rate with super case II transport and poloxamer tablets (F6) follow higuchi with non-fickian diffusion. It is concluded that mucoadhesive formulations of lamivudine can be prepared for sustaining its release. And the successful outcome of the present study also encourage for further studies to assess the ability of the mucoadhesive formulations of lamivudine in providing an effective sustained and safe therapy for AIDS.
very easy and led to the efficient entrapment of drug as well as formation of spherical particles ranging from 250 500 nm. Some process variables like effect of gliadin concentration and effect of surfactant were also evaluated with respect to their % drug entrapment and % yields. The maximum % drug entrapment and % yield were about 73 and 88%, respectively. The sustainedrelease behavior of gliadin nanoparticles were evaluated both in phosphate buffer saline (pH 7.4) and simulated gastric fluid (pH 1.2), respectively, at 37±±±±±1°. Their mucoadhesive properties were determined by in vitro and in vivo methods. The shelf life of prepared nanoparticles was determined by storage at various temperatures while assessed in simulated gastric fluid (pH 1.2) with and without enzyme.
Compositions of various batches of acyclovir GR for- mulations are summarized in Table 1. Hydrophilic, mucoadhesive, polymer matrix tablets were prepared via the wet granulation method. Acyclovir, polymer(s), and microcrystalline cellulose were weighed (electronic weigh- ing balance: AG204; Mettler-Toledo International Inc, Columbus, OH, USA/GP8201; Sartorius AG, Gottingen, Germany) and sifted together through a #40 ASTM sieve and blended in a polybag for 5 minutes. This blend was then granulated manually using a binder solution prepared by dis- solving povidone K 30 in isopropyl alcohol. The wet mass was dried in a tray dryer for 60 minutes at 50 ° C to obtain loss on drying of ,2% w/w (IR moisture analyzer-MA 100, Sartorius AG, Germany). The dried mass was passed through a #20 ASTM sieve to form granules. The resultant granules were lubricated by blending with magnesium stearate (previously sifted through a #60 ASTM sieve) in a polybag. This lubricated blend was compressed manually (tablet press model CMD3-16, Cadmach, India) using a 19 mm × 9 mm, modified capsule-shaped, concave, plain punch with beveled edges.
the venlafaxine loaded microcapsules was carried out in Sprague-Dawley rats by forced swim test. To carry out the study the animals were divided into four different groups (n=6), as control, naïve, pure drug treated and microcapsules treated. The animals were provided with housing in polypropylene cages having artificial lighting to simulate the day-night cycles, and access to food (Lipton pellet diet, Mumbai, India) and water ad libitum. As per the test protocol, the forced swimming test was performed two days prior to the administration of the treatment to induce the depression in animals. It is a common behavioral test where rodents were subjected to force swimming for assessing the depression and testing the efficiency of antidepressant drugs. The animals were allowed for swimming in a plexiglass cylinder (18 cm width and 40 cm height) containing water for 15-20 min till the animals get immobilized, which is an indication of depression like state. The swimming practice in the animals were carried out for 2 days, and then on the third day clinically effective doses of antidepressant drugs were administered prior to 5 min of test swimming session. The animals receiving the test formulations containing drug loaded mucoadhesive microcapsules were observed for total taken to become immobilize compared with other groups. The attentions were made for false positive results do occur due to the generalized increase in motor activity in the animals. The test was performed in replicates to get confirmatory results.
The ophthalmic in-situ gels now days proved an palpable sustained drug delivery in various eye diseases. The formulation of in-situ gels for eye which carries the advantages like easy for administration, reduces frequency of dose and improves patient compliance. The formation of in-situ gels depends on phase transition system or sol-gel transition system. The formulation approaches like temperature intonation, pH change and presence of ions from which the drug gets released in a sustained and controlled manner are utilised for in-situ gels. Various polymers that are used for the formulation of in-situ gels include chitosan, Pluronic F-127, poly-caprolactone, gellan gum, alginic acid, xyloglucan, pectin etc .
Preformulation studies were also carried out to check the compatibility between drug and various polymers using FTIR Spectrophotometer (Perkin-Elmer FTIR Spectrophotometer, USA). Spectra of samples were obtained using Perkin-Elmer spectrophotometer. The FTIR spectra of drug with other excipients were compared with standard FTIR spectra of drug. Several preformulation trials were undertaken for various proportions of drug and polymer by variation of the ethanol and dichloromethane volumes for qualitative and quantitative determination of microsphere characteristics. It was found that hydroxypropyl methylcellulose K4M microspheres show desirable high drug content, yield, floatation and adequate release characteristics and hence was suitable for development of a CR system. FTIR spectra show C-N stretching-1039.67, C=N stretching-1564.72, CH 2 Scissoring-
The objective of the present study was to develop double layered tablets of lornoxicam, a highly potent non- steroidal anti-inflammatory drug. Double layered tablets compris of fast release layer and a sustainedrelease layer, anticipating the rapid drug release that starts in the stomach rapidly alleviate the symptoms and continuous in the intestine to maintain the prolonged analgesic effect. Double layered tablets are characterized by initial drug release in the stomach and comply the requirements of sustainedrelease portion of the dosage form. An inclusion complex of lornoxicam with β-cyclodextrin at 1:2 (drug: β-CD) molar ratio, was incorporated in the fast release layer to increase the release rate of lornoxicam in the stomach to produce rapid analgesic effect. Hydroxy propyl methyl cellulose (HPMC), a hydrophilic matrix forming agent, was integrated in the sustainedrelease layer to provide the sustainment of drug release, F2 was selected as the best formulation as it fulfilled all the criteria. The drug release of F2 extended up to 12 h period. Based on the statistical analysis the drug release follows Anomalous diffusion mechanism. Two months of short term stability study were carried out at 30 ± 2°C / 65 ± 5% RH and 40 ± 2°C / 75 ± 5% RH for the best selected formulation. The results showed that there were no significant changes in all the parameters evaluated for the best formulation.
Extended Release Dosage Forms: Extended release products are formulated to make the drug available over an extended period after administration. This allows a reduction in dosing frequency compared to a drug presented as a conventional dosage form (e.g. as a solution or an immediate-release dosage form). No definition for controlled release or targeted release is provided by the FDA or pharmacopoeias. Extended- release products offer 3 potential benefits: sustained blood levels, attenuation of adverse effects, improved patient compliance. Extended-release products contain a higher drug load and thus any loss of integrity of the release characteristics of the dosage form has potential problems. Extended release can be achieved using sustained- or controlled-release dosage forms. Sustainedrelease: Sustainedrelease dosage forms are those dosage forms which are designed to release drug continuously at sufficiently slow / controlled rate over an extended period of time, thus maintaining a minimum effective concentration (MEC) of the drug in the blood at a constant level throughout the treatment period and provide prolonged therapeutic effect after administration of a single dose.
The present investigation focused on the improvement of the absorption and bioavailability of Metformin HCl along with sustained action. To meet the above criteria Controlled release tablets of Metformin HCl were formulated with hydrophilic swellable rate controlling polymers such as Sodium alginate and HPMC as key excipients.
The difference in the drug release characteristics of the various spheres are due to the differences in the porosity of the coat formed and its solubility in the dissolution fluid. Among all the batches, the F8 (Drug: Sodium alginate: kharaya gum=1:0.75:0.75) batch considered to be the optimized formulation (T50%=2Hrs, T75%=5hrs, T90%=8Hrs), because among all the batches it shows better extent of the drug release, good entrapment efficiency (87%) and in vitro wash-off test showed good mucoadhesive property. Atomoxetine release from the optimized formulation (F8) was slow and extended over a period of 10hrs and these drug loaded spheres were found suitable for the oral controlled release.
The mucoadhesion of sodium alginate-carbopol 934P loaded metronidazole mucoadhesive microcapsules varied from 47.00% ± 0.04% to 61.00% ± 0.03% and 58.00% ± 0.02% to 64.00% ± 0.01% at lower and higher levels of polymer to drug ratio, respectively, with lower and higher sodium alginate ratio were used for lower and higher levels of carbopol 934P polymer concentration. But a medium level of carbopol 934P to drug ratio, as sodium alginate gradually increased, drug entrapment efficiency was also observed an increase from 61.00% ± 0.01% to 63.00% ± 0.07%. Therefore, metronidazole mucoadhesive microcapsules were observed that mucoadhesion was higher when polymer concentration was achieved higher levels due to higher level formulations have more viscosity. Similarly, Nagda et al. (2008) also reported that as polymer concentration was increased, it leads to increased mucoadhesion and percentage mucoadhesion was lower than present work after 8 hours. In vitro dissolution studies of metronidazole mucoadhesive microcapsules
The objective of this study was to formulate and evaluate gastroretentive mucoadhesive microspheres of Cyproheptadine hydrochloride using mucoadhesive polymers. It was expected that gastroretention and mucoadhesion would result in sustainedrelease of the drug thereby providing this formulation as a potential candidate for reducing the dosing frequency of Cyproheptadine hydrochloride. The mucoadhesive microspheres of Cyproheptadine hydrochloride were formulated by orifice ionotropic gelation method using blend of sodium alginate and different concentrations of mucoadhesive microspheres such as carbopol 934P, sodium carboxy methyl cellulose and hydroxy propyl methyl cellulose E5. The microspheres were Evaluated for percentage yield, particle size, shape and surface morphology, entrapment efficiency, swelling index, mucoadhesivity, in-vitro drug release and stability studies. The microspheres formed were discrete, spherical and free-flowing and the size ranged from 500-960 µm. The drug entrapment efficiency was found to be in the range of 54.28% to 90.14%. The IR spectroscopy studies confirmed no major interaction between the drug and the excipients. The optimum formulation was found to be F4 with in-vitro release rate of 92.48% in 10 hours. It was revealed that the drug release from microspheres was diffusion controlled and followed first order kinetics. Stability studies were carried out on the optimum formulation F4 which indicated that there was no change in the particle size and entrapment efficiency of the drug. In the present work it was concluded that gastroretentive mucoadhesive microspheres forms an effective drug delivery system for Cyproheptadine hydrochloride in reducing the dosing frequency and hence improving patient compliance.