ABSTRACT: Nimodipine is a dihydropyridine calcium channel blocker developed for the treatment of high blood pressure. Nimodipine has a half-life of 8-9 h, the bioavailability of 13% and it has narrow absorption window in upper part of the gastrointestinal tract (GIT), hence floating drug delivery system (FDDS) is preferred. During the study, nimodipine encapsulated floating tablets were formulated and characterized for enhancing residence time of drug in GIT. Thus it is decided to prolong the gastric residence time in terms of making floating gastro retentive drug delivery system to increase drug absorption and hence bioavailability. Totally 12 formulations were formulated by using the above drugs by using two different techniques like Effervescent floating technique and Non Effervescent floating technique. Among them Formulations F1-F6 were formulated by using Effervescent floating technique and formulations F7-F12 were formulated by Non Effervescent floating technique. All the formulations were evaluated for the pre compression and post compression parameters and all the formulations shows acceptable limits. The in vitro drug release profiles of the formulations F1-F12 the maximum drug release was found in the F12 formulation containing HPMC K200M(90mg) as a rate retarding polymer by using Non-Effervescent floating technique.
The advance involved in the formulation of floating dosage forms is cherished mixing of drug with a liquefy forming hydrocolloid, which swell in contact with gastric fluid after oral administration and maintains a relative integrity of shape and a bulk density of less than one within the outer gelatinous barrier as shown in figure 7a. The air entrapped by the swollen polymer confers buoyancy to these dosage forms. The gel structure acts as a reservoir for sustained drug release since the drug is slowly released by a controlled diffusion during the viscous barrier. Commonly used excipients, here are gel- forming or highly swellable cellulose type hydrocolloids,
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The gastroretentive drug delivery systems can be retained in the stomach and assist in improving the oral sustained delivery of drugs that have an absorption window in a particular region of the gastrointestinal tract. These systems help in continuously releasing the drug before it reaches the absorption window, thus ensuring optimal bioavailability. Thus, there is a need to maintain Carvedilol Phosphate at its steady state plasma concentration. Hence, the study was carried out to formulate and evaluate Floating dosage form of Carvedilol Phosphate as a model drug and had a aim that final batch formulation parameters should shows prolong drug release. Development of dosage form depends on chemical nature of the drug/polymers, matrix structure, swelling, diffusion, erosion, release mechanism and the in vivo environment. It is an important issue is to design an optimized formulation with an appropriate dissolution rate in a short time period and minimum trials. Many statistical experimental designs have been recognized as useful techniques to optimize the process variables. For this purpose, response surface methodology (RSM) utilizing a polynomial equation has been widely used. Different types of RSM designs include 3-level factorial design, central composite design (CCD), Box-Behnken design and D-optimal design. Response surface methodology (RSM) is used when only a few significant factors are involved in experimental optimization.
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Floating drug delivery systems (FDDS) have a bulk density less than gastric fluids and so remain buoyant in the stomach without affecting the gastric emptying rate for a prolonged period of time. While the system is floating on the gastric contents, the drug is released slowly at the desired rate from the system. After release of drug, the residual system is emptied from the stomach. This results in an increased GRT and a better control of the fluctuations in plasma drug concentration.
2. Ray-Neng C, Hsiu-O H, Chiao-Ya Y, Ming- Thau S, Development of swelling/floating gastroretentive drug delivery system based on a combination of hydroxyethyl cellulose and sodium carboxymethyl cellulose for Losartan and its clinical relevance in healthy volunteers with CYP2C9 polymorphism. European Journal of Pharmaceutical Sciences, 2010 Nov; 10(39): 82–89.
Available online: https://edupediapublications.org/journals/index.php/IJR/ P a g e | 1797 So for increasing the gastric retention time of the some poorly acidic absorption drugs were selected for increasing the gastric retention time for increasing the bioavailability of the drug. From the results obtained it was concluded that the the in vitro drug release profiles of the formulations F1-F12 the maximum drug release was found in the F12 formulation containing Polyx WSR(90mg) as a rate retarding polymer formulated by using Non Effervescent floating technique.
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In oral products, hypromellose is primarily used as a tablet binder, in film-coating, and as a matrix for use in extended-release tablet formulations. Concentrations between 2% and 5% w/w may be used as a binder in either wet- or dry-granulation processes. High-viscosity grades may be used to retard the release of drugs from a matrix at levels of 10–80% w/w in tablets and capsules. Hypromellose is also used in liquid oral dosage forms as a suspending and/or thickening agent at concentrations ranging from 0.25–5.0%. Depending upon the viscosity grade, concentrations of 2–20% w/w are used for film-forming solutions to film-coat tablets. Lower-viscosity grades are used in aqueous film-coating solutions, while higher- viscosity grades are used with organic solvents. Hypromellose is used as an emulsifier, suspending agent, and stabilizing agent in topical gels and ointments. As a protective colloid, it can prevent droplets and particles from coalescing or agglomerating, thus inhibiting the formation of sediments.
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Gastro retentive drug delivery is an approach to prolong gastric residence time, thereby targeting site- specific drug release in the upper gastrointestinal tract (GIT) for local or systemic effects. Gastro retentive dosage forms can remain in the gastric region for long periods and hence significantly prolong the gastric retention time (GRT) of drugs.  Floating systems or hydrodynamically controlled systems are low-density systems that have sufficient buoyancy to float over the gastric contents and remain buoyant in the stomach without affecting the gastric emptying rate for a prolonged period of time.  Comprehensive knowledge about GI dynamics such as gastric emptying, small intestine transit, colonic transit, etc. is the key for the optimum design of oral controlled release dosage forms. The rate and extent of drug absorption from different sites of GI tract and factors that govern the absorption further assist the design of dosage form.
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The release rate of Quinapril from floating tablet was determined using the United States Pharmacopoeia (USP) dissolution testing apparatus II. The dissolution test was performed using 900ml of 0.1 N HCL, at 37 ± 0.50C and 50 rpm. The samples were taken at pre- selected time intervals with replacement of equal volume of dissolution medium.
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From the drug release studies of the gastro retentive floating tablets of loratadine formulated by Non effervescent technique the maximum amount of drug release was found in F15 formulation containing karaya gum(90mg) as a rate retarding polymer as it has higher efficiency for the drug release in the dissolution medium. As we are formulating the gastroretentive floating tablets our main aim was to release the maximum drug in the gastric medium, so by comparing the dissolution profiles of F1-F18 the maximum drug release was found in the F15 formulation than the F6 formulation containing karaya gum in higher concentration formulated by using Effervescent floating technique.
Kannan C 45 et al., (2010) studied gastro-retentive rosiglitazone maleate floating tablets with various materials like hydroxy propyl methyl cellulose (HPMC) K4, K15, K100 were used for its gel forming and release controlling properties, sodium bicarbonate act as a effervescent agent and hydrophobic meltable material like bees wax formulated by melt granulation technique. The formulation F7 containing HPMC K15M and K100M shows sustained release profile and releases upto 12 h and it shows good buoyancy and total floating time. Floating tablets with sustained release characteristics offer critical advantages such as, site specificity with improved absorption and efficacy.
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Development of Gastro retentive floating drug delivery of Silymarin tablets is to provide the drug action up to 12 hours. Gastro retentive floating tablets were prepared by direct compression method using various polymers like Ethyl cellulose, HPMC K4M, Sodium CMC, Carbopol p934. The formulated gastro retentive floating tablets were evaluated for different parameters such as drug excipient compatability studies, weight variation, thickness, hardness, content uniformity, In vitro Buoyancy studies, In vitro drug release studies performed in 0.1N HCL for 12 hrs and the data was subjected to zero order, first order, Higuchi release kinetics and karsmayer peppas graph. The following conclusions could be drawn from the results of various experiments.
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M10 80 - - 20 - 20 - 10 M11 80 - - 20 - 40 - 10 M12 80 - - - 20 20 - 10 M13 80 - - - 20 40 - 10 M14 80 - - - 20 20 15 10 M15 80 - - - 20 40 30 10 M16 80 - - - 20 20 10 10 M17 80 - - - 20 20 05 10 Table 01: Composition of Gastro Retentive Floating Tablets of Famotidine Note: All the quantities are expressed in terms of milligrams. Each formulation contains 40 mg of Famotidine, 0.5% of talc and 1% of magnesium steartae. Table 02: Results of Evaluation Gastro retentive Floating Tablets of Famotidine Formulation code Hardness (kg/cm2) Friability (%) Drug content (%) Average weight (mg) Buoyancy Lag Time ( Sec ) Total Floating Time (hrs) M1 4.65 0.62 97.62 91.7±2.3 60 Sec 24 M2 4.36 0.63 98.87 113±7.5 90 Sec 24 M3 4.93 0.55 99.37 155.9±4.8 95 Sec 24 M4 4.58 0.58 97.37 91.85±6.8 75 Sec 24 M5 4.45 0.72 99.40 113.35±2.9 100 Sec 24 M6 4.76 0.68 99.62 155.75±5.4 102 Sec 24 M7 4.83 0.62 100.85 91.3±5.8 80 Sec 24 M8 4.98 0.65 99.07 113.25±9.7 105 Sec 24 M9 4.98 0.56 97.45 155.2±4.8 120 Sec 24 M10 5.06 0.54 98.62 173.4±2.8 10 Sec 24 M11 4.86 0.58 99.15 193.05±7.8 07 Sec 24 M12 4.95 0.65 100.42 193.2±3.9 05 Sec 24 M13 5.00 0.61 99.72 213.05±8.8 02 Sec 24 M14 4.98 0.63 99.25 173.25±7.3 01 Sec 24 M15 5.02 0.65 99.50 193±7.5 50 sec 24 M16 4.88 0.59 98.97 188.225±6.7 90 sec 24 M17 4.57 0.73 96.65 223.32±7.8 02 Sec 24 Figure 01: Dissolution Profile of Formulation M1 to M10 Gastro Retentive Floating Tablets of Famotidine Figure 02: Dissolution Profile of Formulation M11 to M17 Gastro Retentive Floating Tablets of Famotidine Formulation Code HPMC K4M HPMC K15M HPMC K100M Lactose MCC Sodium bicarbonate Citric acid PVP K30 M1 40 - - - - - - 08
Carvedilol (CVD) is an antihypertensive agent with short elimination half-life, pH-dependent solubility, and narrow absorption window. So, the present study aimed to prolong its gastric residence time that entailed a development of an optimized gastro retentive floating tablets (GRFTs) using 3 2 full factorial design. The tablets were fabricated by direct compression using hydroxypropyl methylcellulose and carbopol 940 as release retarding polymers. The quality attributes of the tablets were evaluated. The buoyancy lag time, total floating time, swelling ability and in vitro release studies were also carried out in 0.1 N HCl (pH 1.2) at 37 ± 0.5 °C. Statistical data analysis revealed that the optimized formulation containing 21.91% HPMC and 15% carbopol 940 had acceptable hardness, optimum floating behavior and 24h controlled-release pattern. The design succeeded to develop CVD-GRFTs with floating ability and controlled release behavior that could improve its solubility, and improve its availability at the best absorptive site.
All the floating matrix tablet formulations were developed by effervescent technique, in which sodium bicarbonate induces carbon dioxide generation. The in vitro buoyancy of floating matrix tablets was induced by sodium bicarbonate and citric acid in the appropriate concentration in presence of dissolution medium in optimized ratio without compromising the matrix integrity with the possible shortest lag time and buoyancy duration of up to 16 h. It was observed that the gas generated was trapped in the tablet and was protected within the gel formed by hydration of polymers, thus decreasing the density of the matrix tablet below 1, and the tablet became buoyant. Higher viscosity grade of hydroxypropyl methyl cellulose (HPMC K15M) in the formulations was used to obtain viscous gel to prevent the air bubble from rupture. By using this type of HPMC, stable and persistent buoyancy was achieved. All the developed formulations swelling behavior was observed radially and axially during in vitro buoyancy studies. The effervescent floating matrix tablets containing HPMC K15 exhibited buoyancy lag time of 50 to 75 seconds and floated up to16h, while the floating effervescent matrix tablets containing Pullulan gum exhibited buoyancy lag time of 30 to 50 seconds and floated up to 8h and the floating effervescent matrix tablets containing HPMC K15M and Pullulan gum exhibited buoyancy lag time of 40 to 55 seconds and floated up to 14h and mean values of each formulations were represented in Table 4. These results shows that the formulation containing higher amount of HPMC K15M has moderate floating lag time and more total buoyancy in comparison to the formulations containing higher amount of Pullulan Gum. It is evident from the in vitro release data that increase in HPMC K15M concentration decrease in the drug release and also increased in the floating duration, probably due to viscous gel formation.
Carbomers are used in liquid or semisolid pharmaceutical formulation as rheology modifiers. Formulations include creams, gels, lotions and ointments for use in ophthalmic, rectal, topical and vaginal preparations. carbomer grades with residual benzene content greater than 2ppm do not meet the specifications of the PhEur 6.4 monograph. However, carbomer having low residual of other solvent than the ICH-defined class IOVI solvents may be used in europe. Carbomer having low resuidals of ethl acetate, such as carbopol 971 P NF or carbopol 974PNF may be used in oral preparations, in suspensions, capsules or tablets. In tablet formulations, carbomer are used as controlled release agents and/or as blinders. In contrast to linear polymers, higher viscosity does not results in slower drug release with carbomers . Lightly cross linked carbomers are generally more efficient in controlling drug release than highly cross linked carbomers. In wet granulation processes, water, solvents or their mixtures can be used as the granulating fluid. The tackiness of wet mass may be reduced by including talc in the formulation or by adding certain cationic species to the granulating field. However the presence of cationic salts may accelerate the drug release rates and release rates and reduce bioadhesive properties. carbomer polymers have also been investigated in the preparation of sustained –release matrix beads, an enzime inhibitors of intestinal proteass in peptide –containing dosage forms as a bioadhesive for a cervical patch and for intranasally administered microspheres in magnetic granules for site-specific drug delivery to the esophagus, and in oral mucoadhesive controlled drug delivery systems. Carbomer copolymers are employed as emulasifying agents in the preparation of the oil-in water emulsion for external administrarion. carbomer 951 has been investigated as a viscosity increasing aid in the preparation of multiple emulsion microspheres. Carbomers are also used in cosmetics. Therapeutically carbomer formulation have been provided efficacious in improving symptoms of moderate to severe dry eye syndrome
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system gets emptied from the stomach. This results in an increased gastric retention time and a better control of the fluctuations in plasma drug concentration. However, besides a minimal gastric content needed to allow the proper achievement of the buoyancy retention principle, a minimal level of floating force is also required to keep the dosage form reliably buoyant on the surface of the meal. 
Gastro retentive systems can remain in the gastric region for several hours and hence significantly prolong the gastric residence time of drugs. Prolonged gastric retention improves bioavailability, reduces drug waste, and improves solubility for drugs that are less soluble in a high pH environment. It has applications also for local drug delivery to the stomach and proximal small intestines. Gastro retention helps to provide better availability of new products with new therapeutic possibilities and substantial benefits for patients.
Herpes simplex virus (HSV) is a member of family of herpes viridae, a DNA virus. There are two types of Herpes Simplex Viruses (HSV). Viz HSV type 1 and type 2. HSV type 1 is the herpes virus that is usually responsible for cold sores of the mouth, the so called “fever blisters”. HSV type 2 is the one that most commonly causes genital herpes. Currently the treatments available for herpes simplex are conventional tablets and topical gel for application on outbreaks. The drugs that are commonly used for herpes simplex are Acyclovir, Valaclovir and Famciclovir. Acyclovir, the first agent to be licensed for the treatment of herpes simplex virus infections, is the most widely used drug for infections such as cutaneous herpes, genital herpes, chicken pox, varicella zoster infections. Acyclovir is currently marketed as capsules (200 mg), tablets (200, 400 and 800 mg) and topical ointment. Oral acyclovir is mostly used as 200 mg tablets, five times a day. The presently available conventional therapy is associated with a number of drawbacks such as highly variable absorption and low bioavailability (30%) after oral administration. The main problem with the therapeutic effectiveness of acyclovir is its absorption, which is highly variable and dose dependent thus reducing the bioavailability to 30% and half life is 3 hrs. Acyclovir is soluble in acidic pH and is predominantly absorbed from stomach. 
The drug release profiles of the MTX formulations showed the inability of TSP powder in sustaining release when it was used alone or in combination with low concentra- tions of xanthan. This shows the failure of TSP to produce a uniform and strong gel which caused the rapid drug release, this might be due to slow hydration of the TSP matrix to form a thick gel layer, but the result of salep and TKP shows when these polymers are exposed to aqueous medium, it undergoes rapid hydration and chain relaxation to form a viscose gelati- nous layer to control the release. Only MTX4 and MTX5 were able to control the release for 12 hours. These results indicated that MTX4 which had the highest similarity factor (f 2 = 61%) with the commercial formulations was the optimum formulation of this batch. The intact formulations remained floating for more than 24 hours (Figure 5).
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