Bilayer Tablets

Wet granulation is the most widely used to prepare tablets. Formulation with different binders was compressed into tablets. The required quantities of Telmisartan ,starch ,lactose monohydrate ,HPMC K4M, crospovidone were weighed accurately using analytical balance and were mixed well using laboratory conditions. The aqueous binder solution was added and mixed thoroughly to form dough mass. Carmiosine Colour was added to the aqueous binder solution for Telmisartan granules to provide visual detection of two different layers in the bilayer tablets. The formed mass was passed through Mesh no.12 to obtain wet granules .The wet Granules were dried in a hot air oven at 300 c temperatures. then the dried granules were passed through mesh no.16 to break aggregates. Talc & magnesium stearate were passed through mesh no.100 on to dry granules and blended in a polyethylene bag .The Tablet granules were then compressed using compression machine at punch No. 5 (11,15) .

tablets to break up on exposure to water and rapidly release any active ingredients. The initial release of guaifenesin from the formulations with low concentration of HPMC 2208 in GBT-HPMC (6 % w/w) and GBT-HPMC (8 % w/w) was high (> 75 % in two hours) compared to the drug release (65 % in two hours) and (57 % in two hours) from GBT-HPMC (10 % w/w) and GBT-HPMC (14 % w/w), respectively. This is mainly because of release of guaifenesin from the IR layer and also drug release from the surface of SR layer due to the small channels found underside of individual 3D printed bilayer tablets (Fig. 2c (viii)). The drug release of guaifenesin from GBT-HPMC (14 % w/w) was the closest to the commercial GBT. This is consistent with the increased amount of hydrophilic matrix material used (HPMC 2208) (14 % w/w). Finally, the release rate of guaifenesin release decreased as the concentration of HPMC 2208 was increased. This increase in concentration of HPMC is expected to lead to improved wettability, enhanced water uptake and greater swelling of the hydrophilic matrix and gel barrier formation which is all consistent with the observed reduction in drug release rate from the formulation with greater amounts of HPMC 2208 (Fig. 2c (iv & v)) and (Fig. S.2) (Folttmann and Quadir, 2008).

The present work was aimed towards developing a bilayer tablets containing Glimepiride as immediate release and Metformin HCl as sustained release. The tablets were prepared using techniques of wet granulation and compression. The optimization of the tablets was done based on experimental result such as its physiochemical parameters, dissolution and content uniformity. The tablets produced were stable and reliable. The result suggested that various variables affecting the dissolution of the tablets. Formulation F6 shows better dissolution. So it is suggested that for highly water soluble drug like Metformin HCl, it is desirable to use combination of different polymer for sustained release layer and incorporation of superdisintegrant like SSG in immediate release layer. The release data further indicated that combination of SCMC and HPMC K 100M can give the sustained release effect followed by the initially burst release effect due to the superdisintegrant SSG in immediate release layer. HPMC K100M polymer controlled the release of Metformin HCl up to 10 hrs intended for once daily administration. The release data of in vitro study indicates that formulation follows zero order, Higuchi equation and diffusion takes place via non-fickian transport. Formulation F6 found to be stable at accelerated stability as per the ICH guidelines for a period of 3 months.

Stability studies are an integral part of the drug development program & are one of the most important areas in the registration of Pharma products. The purpose of stability testing is to provide evidence on how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors such as temperature, humidity & light & enables recommended storage conditions, re-test periods and self half lives to be established. Stability assessment starts with studies on the substance to determine degradation products degradation pathway. In these types of studies the product is analyzed at intervals for various parameters which may include assay of active ingredient, measurement of known degradation products, hardness, dissolution time, appearance, etc., Omeprazole and Domperidone Bilayer tablets were packed in HDPE containers and evaluated for accelerated stability studies at 40ºC/75% RH conditions.

aspartame, magnesium stearate and D-mannitol were procured from SD Fine Chem., Mumbai. Preparation of buccal tablets: Direct compression method has been employed 8 to prepare buccal tablets of GRN using sodium CMC, HMPC 15 cps and Carbopol 934 p as polymers. Method: All the ingredients including drug, polymers and excipients were weighed accurately according to the batch formula (Table 1). The drug is thoroughly mixed with mannitol on a butter paper with the help of a stainless steel spatula. Then all the ingredients except lubricant were mixed in the order of ascending weights and blended for 10 min in an inflated polyethylene pouch. After uniform mixing of ingredients, lubricant was added and again mixed for 2 min. The prepared blend (100 mg) of each formulation was pre-compressed, on 10-station rotary tablet punching machine (Clit, Ahmedabad) at a pressure of 0.5 ton for 30 s to form single layered flat-faced tablet of 9 mm diameter. Then, 50 mg of ethyl cellulose powder was added and final compression was done at a pressure of 3.5 tons for 30 s to get bilayer tablet. Compositions of the designed bilayer tablets are given in Table 1.

The aim of present study was to design the concept of bilayered tablets containing Pioglitazone hydrochloride for immediate release using cross Povidone as super disintegrant and Metformin hydrochloride for sustained release using EUDRAGIT ESPO as matrix forming polymer. The tablets were evaluated for physicochemical properties. All the values are found to be satisfactory. In vitro release studies were carried out as per USP in pH 1.2 and phosphate buffer pH 6.8 using the USP apparatus II. The release kinetics of Metformin hydrochloride was evaluated using the regression coefficient analysis. The formulated tablets (F5) shows first order release and diffusion was the dominant mechanism of drug release. The polymer EUDRAGIT ESPO had significant effect on the release of Metformin HCl matrix tablets (F5).Thus formulated bilayer tablets proved immediate release of Pioglitazone and Metformin HCl as sustained release over a period of 12 hours. The stability studies and FT-IR studies were also indicating the absence of strong interactions between the components and suggesting drug-excipient compatibility in all the formulations examined.

In- vitro buoyancy studies revealed that tablets of hardness 2-4 Kg/cm2 after immersion into the floating media floated immediately, tablets with hardness of 4-5 Kg/cm2 sank for 3-4minutes, and then floated on to the surface. Tablets with different hardness remained floating for 8-12 hrs. The buoyancy of the tablets is governed by both the swelling of the poly hydrocolloid particles in the tablet surface when it the contacts the gastric fluids and presence of the internal voids in the centre of the tablet, hence altering a bulk density <1. The formulation F17 formulated with HPMC K 100 M sustained the release for 12 hrs, when compared with formulations made with HPMC K4 M and HPMC K5M grade of polymers this may be due to the viscosity of the polymer i.e. formation of gel structure. Finally concluded that, results of the studies based on the in- vitro performance clearly suggested that, sustained release floating bilayer tablets can be prepared by immediate release layer of drug with Sodium Starch Glycollate and SR layer comprises the sodium bicarbonate, with HPMC K 100 M for achieving the sustained action and restricted the drug release in the stomach.

The present research work involve the development of a bilayer tablet of ciprofloxacin hydrochloride using a superdisintegranting agent (sodium starch glycolate) for the fast releasing layer and hydrophobic polymers like ethyl cellulose, acrycoat L100 and acrycoat S100 for the delayed releasing layer. Ciprofloxacin was used as a model drug. Tablets were prepared by wet granulation method. The prepared bilayer tablets were evaluated for angle of repose, bulk density, tapped density, Carr’s index, Hausner’s ratio at the precompression stage and thickness variation, weight variation, hardness, friability, drug content, disintegration time, in vitro drug release study at the post compression stage.. In vitro dissolution studies were carried out in a USP 24 apparatus I. In vitro dissolution kinetics followed the Higuchi model via a non-Fickian diffusion controlled release mechanism after the initial burst release. FT-IR studies revealed that there was no interaction between the drug and polymers. Statistical analysis (ANOVA) showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p < 0.05) in the amount of drug released after 12 h from optimized formulations was observed. Present research work involves the development of a bilayer tablet of ciprofloxacin hydrochloride using a superdisintegrant for the fast releasing layer and hydrophobic polymers for the delayed releasing layer. There was the initial burst effect from the formulations to provide the loading dose of the drug, followed by sustained release to provide maintenance dose of the drug.

The dissolution medium for the bilayer tablets was modified. The dissolution was carried in two steps: Step I: The release of Glyburide was carried out in 7.4 pH phosphate buffer with 8.5% of alcohol and 0.24% tween 80 as the drug is highly insoluble hence the dissolution media was modified as described by El- Massik. et.al. 2006 The temperature was maintained at 37 0 C ± 0.5 0 C in USP I apparatus in 900 ml. 10 ml of the sample was withdrawn, filtered and diluted suitably and analyzed by UV spectrometer at 227 nm 15 . The results are tabulated in table 3.

In recent times, various developed and developing countries move towards combination therapy for treatment of multiple diseases and disorders requiring long term therapy such as hypertension and diabetes. Combination therapy have various advantages over monotherapy such as problem of dose dependent side effects is minimized, a low dose of two different agents reduces the dose related risk, the addition of one agent may potentiate effects of other agent. Using low dosage of two different agents minimizes the clinical and metabolic side effects that occur with maximal dosage of individual component of the combined tablet and thus dose of the single components can be reduced. Bilayer tablets are novel drug delivery systems where combination of two or more drugs in single unit having different release profiles improves patient compliance, prolongs the drugs action, avoid saw tooth kinetics resulting in effective therapy along with better control of plasma drug level. Bilayer tablets are very common dosage form for drugs such as captopril, metoprolol, amoxicillin and potassium clavanate, propanolol hydrochloride, bambuterol hydrochloride. Joint national committee VI recognized the value of combination therapy and suggested that combining drugs with different modes of action will often allow smaller doses of drugs to be used to achive control and minimize the potential dose dependent side effects. JNCvi recomended that the combination of a low dose of two drugs in fixed dose combination is an appropriate choice for initial treatment of any chronic disease. Hence management of multiple diseases can be effectively and better done by bilayer tablet or layering tablet.

Bilayer tablets are type of multiple compressed tablets. Tablets are composed of two layers of granulation and have similar actions or support the action of one layer with another layer prepared by compression. Bilayer tablets require fewer material than compression coated tablets, which weigh less and may be thinner. Bilayer tablet is suitable for sequential use of two drugs in combination, separate two incompatible substances and also for sustained release tablet in which one layer is as initial dose which releases the drug slightly faster rate when compared to another layer and second layer is maintenance dose.

The aim of the present study was to formulate and evaluate a stable immediate release tablet of Tenofovir DF and Lamivudine to maintain constant therapeutic levels of the drug and compare with the innovator samples. The immediate release bilayer tablets were prepared by wet granulation method with different concentrations of CCS & SSG Type-A as superdisintegrants. The formulations F1, F2, F3 and F4 were prepared by dry granulation method. And the drug release of above formulations was slow. In all these formulations only 80% of the drug release was found within 60min for Tenofovir DF and only 90% drug release for Lamivudine within 60 min. The formulation F5 and F6 were prepared by wet granulation method which resulted in increase in dissolution rate of Tenofovir DF and Lamivudine but it was not matching with innovator % drug release.

1. Harika Ryakala, 1 s. dineshmohan, 1 alluri ramesh, 1 and v. r. m. gupta 2 formulation and in vitro evaluation of bilayer tablets of nebivolol hydrochloride and nateglinide for the treatment of diabetes and hypertension journal of drug delivery, 2015. (2015), article id 827859, 14 pages http://dx.doi.org/10.1155/2015/827859

sustained release and Glimepride immediate release matrix tablets as a dosage form by different polymers such as HPMC, Povidone, Lactose Monohydrate, Ethyl cellulose, Microcrystalline Cellulose and study the invitro release patterns of the drug. In the present study bilayer tablets Glimepride prepared by direct compression method and Metformin prepared by wet granulation technology. The prepared tablets were evaluated for various physicochemical parameters such as drug-excipient interaction by FTIR, flow properties, hardness, weight variation, friability, and in vitro dissolution studies optimized based on desired sustained release time (16hrs) and acceptable floating properties The FTIR study revealed that there is no drug-excipient interaction. During preformulation it has been observed that there is no drug- drug and drug excipient interaction, so the excipients which have been selected for the formulation are compatible with the drugs. This system provides zero order or near zero order release for IR layer and SR layer provides Higuchi model.

Morsu Ashok. et al., 47 developed controlled release formulation along with various features to provide a way of successful drug delivery system. Bilayer tablet is better than the traditionally used mouthwash,sprays,gels So use of bilayer tablet is a very different aspect for anti-inflammatory and analgesic. Bi-layer tablet is suitable for sequential drugs in combination, separate two incompatible substances and also for sustained release tablet in which one layer is immediate release as initial dose and second layer is maintenance dose. Bilayer tablet is improved beneficial technology to overcome the shortcoming of the single layered tablet. Several pharmaceutical companies are currently developing bilayer tablet for a variety of reason: patent extension, therapeutic, marketing to name a few. To reduce capital investment quite often existing but modified tablet presses are used to develop such tablets. The present article provides an introduction to bilayer tablet technology, advantages and disadvantages, various techniques, quality and GMP requirements, characterization and evaluation of bilayer tablets. Bilayer tablet, various techniques, bilayer tablet presses, GMP requirements characterization and evaluation of bilayer tablet.

Aim of study was to develop bilayer drug delivery for treatment of spasticity by delivering loading and maintenance dose for fast achievement of peak plasma concentration and maintaining the same respectively. The prepared drug loaded bilayer tablets were evaluated for pre and post compression parameters. Stability study of the promising formulation was also performed. The tablets were prepared by direct compression and wet granulation method. The loading dose was delivered in the form of immediate release layer prepared by different super-disintegrations and maintenance dose was delivered through sustained release layer prepared by using polymers like HPMC K4, HPMC K15M, HPMC K100, PEO WSR 303 and Precirol. Both the immediate release layer and sustained release layers were separately optimized and then combined to optimize the bilayertablets. No interactions were found between drug and excipients. Formulation containing Kyron T314 shows immediate drug release. Formulation Containing PEO WSR 303 shows sustained release action and bilayer formulations F6 shows releases up to 24 hours. Bilayer tablets with release characteristics offer critical advantages such as, site specificity with improved absorption and efficacy.

Preparation of Lornoxicam Bilayer Tablets: Method of preparation of Sustained Release Layer 12 Lornoxicam sustain release layer had been formulated by utilizing direct compression procedure. Weighed quantities of desired weighed of solid medicament other excipients like MCC, Retardant polymer were mixed properly shifted from sieve no 40. Before compression add talc, magnesium stearate mixed it well. Prepared powder blended than punched by using single punch tablet compression machine.

The developments of enhanced oral protein delivery technology by immediate release tablets which may release the drugs at an enhanced rate are very promising for the delivery of poorly soluble drugs high molecular weight protein and peptide. The oral route remains the perfect route for the administration of therapeutic agents because the low cost of therapy, manufacturing and ease of administration lead to high levels of patient compliance 1 . The concept of

The aim of the present study was to design and evaluate bilayer Floating tablets of Metoprolol succinate and Amlodipine besylate. An attempt was made to formulate bi-layer tablet appropriate for delivering different drugs with different release pattern like one layer of drug as IR to get rapid release & 2 nd drug as SR of drug which gives effect of drug for adequate long time and reduce frequency of dose.

Dept. of Pharmaceutics, The Erode College of Pharmacy and Research Institute. Page 26 combination of polymers (such as sodium alginate, HPMC 50 cps and Carbopol 934p) and ethyl cellulose as an impermeable backing layer to release the drug in a unidirectional way toward the mucosa, thus avoiding loss of drug due to wash out by saliva. The designed tablets were evaluated for various physical and biological parameters, drug content uniformity, in-vitro drug release, short-term stability, drug- excipient interactions (FTIR). The formulation SAF with the drug matrix layer 1 composition- sodium alginate (47% w/w), Carbopol 934p (3% w/w), PVP K-30 (binder, 30% w/w) and mannitol (channeling agent, 15% w/w) was found to be promising. This optimized formulation exhibited an in vitro drug release of 94% in 8 h along with satisfactory bioadhesion strength (4.6 gm).Short-term stability studies (40±2 C/75±5% RH for 3 months)