Swami Vivekanand College of Pharmacy, Banur - 140601, Punjab, India.
ABSTRACT: The scenario of pharmaceutical drug delivery are expeditiously challenging, but conventional pharmaceutical dosage forms are still dominating.
Immediaterelease dosage forms are those wherein ≥85% of labeled amount dissolves within 30 min. Superdisintegrants are used to improve the efficacy of solid dosage forms. The basic approach used in the formulation of the tablet is the use of superdisintegrants like croscarmellose, sodium starch glycolate, and crospovidone, etc. These superdisintegrants provide instantaneous disintegration of the tablet after administration in the stomach. Thus, decreasing the disintegration time which in turn enhances drug dissolution rate. The rapid disintegration may be due to the rapid uptake of water from the medium, swelling, burst effect and thereby promoting bioavailability. Tablets formulations are mostly preferred because of the low cost of manufacture, package, shipment, increased stability. Among various dosage forms used for oral drug delivery, tablets are one of the most successful and marketable drug delivery regimens as it provides several advantages over another form of dosage forms. This article provide an exhaustive account illustrating the significances of superdisintegrant in the immediaterelease of tablets and the mechanism of disintegration along with various conventional techniques and novel granulation technology used to prepare immediate-releasetablets.
Pharmacy Discipline, Life Science School, Khulna University, Khulna-9208, Bangladesh
Among the different routes of administration, the oral route of administration continues to be the most preferred route due to various advantages including ease of ingestion, avoidance of pain, versatility and most importantly patient compliance. The different dosage forms include tablets and capsules. Recently immediatereleasetablets have started gaining popularity and acceptance as a drug delivery system, mainly because they are easy to administer and lead to better patient compliance. The present work involves the formulation development, optimization and in-vitro evaluation of immediaterelease allylestrenol tablets. To minimize critical process parameters and since allylestrenol is heat sensitive, direct compression method was selected for the formulation of immediaterelease allylestrenol tablets. Tablets were prepared using cross carmellose sodium, crosspovidone, pre gelatinized starch and sodium starch glycolate as disintegrants. During the course of study it was found that the formula G4 containing sodium starch glycolate as disintegrant exhibited acceptable disintegration time, percentage drug content per tablet and in vitro drug release. So at last it was concluded that immediaterelease allylestrenol tablets can be prepared using direct compression which met the required specifications.
Figure 3: Linear graph comparison between cumulative % drug releases for formulations (F6 &
From the above Table 7, it is observed that the thickness, hardness, weight variation and drug content of the immediatereleasetablets were in the passable range. The F1,F2 and F3 formulations containing menthol as the subliming agent, SSG as super disintegrating agent in the percentage of 4%, 6% and 8% didn’t show much effect on the Disintegration time i.e., 1min 14sec,47sec 38sec respectively and dissolution time i.e., 101% in 40min,98% in 40min and 99% 35min respectively .
The objective of this investigation was to explore application of osmogens as superdisintegrant. Osmotic pressure of a solution is the external pressure that must be applied to the solution in order to prevent it being diluted by the entry of solvent via a process known as Osmosis . Osmosis refers to the process of movement of solvent molecules from lower concentration to higher concentration across a semi permeable membrane. The release rate of a drug from an osmotic system is directly proportional to the osmotic pressure exerted by the core formulation. For controlling the drug release from these systems, it is important to optimize the osmotic pressure gradient between inside compartment and the external environment. It is possible to achieve and maintain a constant osmotic pressure by maintaining a saturated solution of osmotic agent in the compartment . If a drug does not possess sufficient osmotic pressure, an osmogens can be added in the formulation. Osmotic systems utilize the principles of osmotic pressure for the delivery of drugs at constant rate . Drug release from these systems is independent of pH and other physiological parameters to a large extent and it is possible to modulate the release characteristics by optimizing the properties of drug and delivery system . Superdisintegrants are used in the formulation of immediatereleasetablets in order to achieve faster disintegration. In this study an attempt has been made to explore the possibility of use of osmogens as superdisintegrants. The benefits of osmogens over superdisintegrants are its cost effectiveness and compressibility. Moreover, osmogens like dextrose, fructose, sucrose, mannitol, sodium chloride, potassium chloride, etc. have nutritive value for human consumption in daily life. They are effective as tablet superdisintegrants in lower concentration.
Page 102 7. SUMMARY AND CONCLUSION
The aim of this study was to develop stable Escitalopram oxalate ImmediateReleasetablets which have more chances for drop in dissolution during stabiltiy and comparing with marketed product. Escitalopramoxalate comes under the category of Antidepressant and anxiolytic. In this study Escitalopram oxalate tablets were prepared by using a range of excipients including diluents and functional excipients and formulated by direct compression, dry granulation and wet granulation of which direct compression and dry granulation process were failed due to poor content uniformity of dosage form and wet granulation was successful in which non aqueous granulation with non aqueous coating was found to be good which showed very less impurity generation during stability studies. Different invitro studies were performed and were compared with that of reference and the one with wet granulation were found to be satisfactory.
Formulation & development of olmesartan medoxomil immediatereleasetablets Page 20 Buccal tablets:
Tablets designed to dissolve on the buccal (cheek) mucous membrane were a precursor to the ODT. This dosage form was intended for drugs that yield low bioavailability through the digestive tract but are inconvenient to administer parenterally, such as steroids and narcotic analgesics. Absorption through the cheek allows the drug to bypass the digestive tract for rapid systemic distribution. Not all ODTs have buccal absorption and many have similar absorption and bioavailability to standard oral dosage forms with the primary route remaining GI absorption. However, a fast disintegration time and a small tablet weight can enhance absorption in the buccal area. The first ODTs disintegrated through effervescence rather than dissolution, and were designed to make taking vitamins more pleasant for children.
Oral drug delivery has been known for decades as the most widely used route of administration among all the routes that have been explored for the systemic delivery of drugs via various pharmaceutical products of different dosage forms. Montelukast is a leukotriene receptor antagonist used for the maintenance treatment of asthma, chronic asthmatic attacks and to relieve symptoms of seasonal allergies. Its biological half life is 2.5 – 5.5 hrs thereby decreasing bioavailability up to 64%. In order to improve bioavailability, immediatereleasetablets were developed. In the present work the immediatereleasetablets of Montelukast sodium were prepared by direct compression method. Crosspovidone (5, 7.5, 10 w/w), crosscarmellose sodium (5, 7.5, 10 w/w) and sodium starch glycolate (5, 7.5, 10 w/w) were used as super disintegrants in different
Recently immediatereleasetablets have started gaining popularity and acceptance as a drug delivery system, mainly because they are easy to administer, has quick onset of action is economical and lead to better patient compliance. They are also a tool for expanding Nebivolol HCl is a highly selective beta1-adrenergic blocker that leads to vasodilation and decreased peripheral vascular resistance. The present investigation an attempt has made to prepare immediatereleasetablets of Nebivolol Hydrochloride by using Microcrystalline Cellulose PH101 (MCC) as diluent, Pregelatinised Starchas a binder with different superdisintegrants like Crosspovidone (CP), Crosscarmellose Sodium (CCS).The formulation development work was initiated with wet granulation. The prepared granules and tablets were evaluated for various pre and post compression parameters such as loss on drying, bulk density, tapped density, compressibility Index, Hausner’s Ratio, weight variation, thickness, hardness, friability, disintegration time and dissolution studies. Among the formulations, F 7 formulation with 16mg of
This investigation is undertaken with an aim to develop pharmaceutically equivalent, stable, cost effective and quality improved formulation of Clopidogrel bisulphate immediatereleasetablets. The task of developing immediaterelease tablet is accomplished by using a suitable diluents and super-disintegrants. Faster disintegration of the tablet administrated orally minimizes absorption time and improves its bioavailability in less time. ImmediateRelease tablet of Anti plate drug is formulated using direct compression using super disintegrant Croscarmellose Sodium and Crospovidone. The current study involves preparation and evaluation of Clopidogrel bisulphate tablets, comparison of dissolution rate of optimized formulation with innovator’s product and estimation of similarity and difference factors. The formulations were further evaluated for pre & post compression parameters and in-vitro dissolution studies. The study reveals that the formulation F8 is found to be the optimized formulation with 99% drug release in 30 minutes in comparison with other super disintegrants. The kinetics study shows that the fast dissolving tablet formulation followed First order kinetic model explaining the diffusion controlled release mechanism. The similarity and dissimilarity factor obtained for Clopidogrel bisulphate was found to be within the standards. The formulation F8 exhibited similar release profile as that of innovators product at each time point. Hence, F8 was considered as the best formulation.
INTRODUCTION: An immediaterelease dosage form allows a manufacturer to extend market exclusivity while offering patients a convenient dosage form or dosage regimen. ImmediateReleaseTablets are those tablets which are designed to disintegrate and release their medication with no special rate controlling features, such as special coatings and other techniques, 1, 2 immediate releases and fast dispersing drug delivery system may offer a solution to these problems. Recently, immediatereleasetablets have started gaining popularity and acceptance as a drug delivery system, mainly because they are easy to administer, has a quick onset of action is economical and lead to better patient compliance.
KEY WORDS: Pravastatin sodium; immediaterelease; superdisintegrant; Hyperlipidemia; in vitro drug release . INTRODUCTION
Immediatereleasetablets are those, which disintegrate or dissolve fast in saliva without the need of water. This could enhance the clinical effect of drug through pre-gastric absorption from mouth, pharynx and esophagus by avoiding first pass liver metabolism 1 . Due to ease of administration and better patient compliance these drug delivery systems are gaining popularity 2 . Pravastatin sodium, a newer anti hyperlipidemic drug has reported to have extensive first-pass metabolism and also very low half life of 1- 1.5hrs was selected as model drug for the study. The immediatereleasetablets of pravastatin sodium were prepared by using direct compression and wet granulation method. Different formulations were prepared with varying concentrations of binders, super disintegrating agents and lubricants and the optimized formulation was to be found in this present study.
Immediatereleasetablets are those tablets which disintegrate and release the drug rapidly once it enters GIT. Recently immediatereleasetablets have started gaining popularity and acceptance as a drug delivery system, mainly because they are easy to administer and lead to better patient compliance. They are also a tool for expanding markets, extending product life cycles and generating opportunities. Efavirenz is an anti retroviral drug with poor aqueous solubility. The present work involves the formulation development and invitro evaluation of immediaterelease Efavirenz tablets for enhancement of dissolution rate. Direct compression method was selected for the formulation of immediaterelease Efavirenz tablets. Tablets were prepared using different concentrations of Croscarmellose sodium, Crospovidone, and sodium starch glycolate as superdisintegrants. During the course of study it was found that the formula F8 containing Sodium starch Glycolate as superdisintegrant exhibited acceptable disintegration time and in vitro drug release. The Drug-excipient interaction was investigated by FTIR. Later they were subjected to stability studies after packing which showed acceptable results.
Candesartan Cilexetil is an esterified prodrug of Candesartan, a non-peptide angiotensin II type-1(AT1) receptor antagonist used in the treatment of hypertension and congestive heart failure. Candesartan meets the requirement of high potency but it is poorly absorbed when administered orally. Therefore, the prodrug Candesartan Cilexetil is developed. It is soluble in methylene chloride, half life is 5.1 to 10.5hrs and bioavailability is 15%. It is marketed as conventional tablets. In this work, it is formulated as immediatereleasetablets by changing the concentration of ingredients. For many drug substances, conventional immediate-release formulations provide clinically effective therapy while maintaining the required balance of pharmacokinetic and pharmacodynamic profiles with in acceptable level of safety to the patient. The immediaterelease formulation of Candesartan Cilexetil is prepared by wet granulation method to provide rapid onset of action. In order to optimize the best formulation, ten different trials are developed. The main ingredients used in the formulation are lactose monohydrate, PEG, calcium CMC and MCC. Weight variation, thickness, friability, disintegration time, in-vitro release, pharmaceutical assay are studied as response variables. The formulation containing 38% of MCC is selected as an optimized product in which the different physical properties and in-vitro release profile showed best comparable results with innovator product.
Cataflam Immediate-ReleaseTablets in Analgesia/Primary Dysmenorrhea: The analgesic efficacy of Cataflam was demonstrated in trials of patients with postoperative pain (following gynecologic, oral, and orthopedic surgery), osteoarthritis of the knee, and primary dysmenorrhea. The effectiveness of Cataflam in studies of pain or primary dysmenorrhea showed that onset of analgesia began, in some patients, as soon as 30 minutes, and relief of pain lasted as long as 8 hours, following single 50-mg or 100-mg doses. Duration of pain relief was judged by the time at which approximately half of the patients needed remedication. The onset and duration of pain relief for either the 50-mg or 100-mg dose was essentially the same, whether patients had moderate or severe pain at baseline.
Immediaterelease solid oral dosage forms are classified as either having rapid or slow dissolution rates. Immediaterelease dosage forms are those for which ≥85% of labeled amount dissolves within 30 min. For immediatereleasetablets, the only barrier to drug release is simple disintegration or erosion stage, which is generally accomplished in less than one hour .
The results are shown in Table. No: 9.
In - Vitro drug release study
Standard USP apparatus have been used to study in vitro release profile using rotating paddle.
In-vitro release rate study of immediatereleasetablets of Prasugrel hydrochloride were carried out using 900ml of phosphate buffer pH6.8, at 37±0.50c at 50 rpm. A sample (5ml) of the solution was withdrawn from the dissolution apparatus at 5, 10, 15, 20 & 30 min and withdrawn volume was replaced with fresh dissolution media. The withdrawn samples were diluted with dissolution medium and then filtered with whattman filter paper and assayed at 249 nm. The results are shown in Table. No: 10 & 11.
Keywords: Immediaterelease; Explotab; Solutab; Polyplasdone XL
An immediaterelease dosage form allows a manufacturer to extend market exclusivity while offering patients a convenient dosage form or dosage regimen. ImmediateReleaseTablets are those tablets which are designed to disintegrate and release their medication with no special rate controlling features such as special coatings and other techniques [1, 2] , immediate releases and fast dispersing drug delivery system may offer a solution to these problems.
RESULTS AND DISCUSSION
The main objective of the present research work was to develop a stable formulation of Olmesartan tablets in line with reference product. At initial stage, solubility analysis was done to find out solubility of Olmesartan Medoxomil. Drug-excipient compatibility study was performed to evaluate the compatibility of active pharmaceutical ingredient with excipients. Formulation of immediatereleasetablets of Olmesartan Medoxomil was done by direct Compression, slugging-deslugging and wet Granulation technique but the final formulation was prepared by wet Granulation
Tenofovir Disoproxil fumarate immediatereleasetablets Experimental Work
Adhiparasakthi College of Pharmacy, Melmaruvathur Page 100 Objective of the study:
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 and light, enabling recommended storage conditions, re-test periods and shelf-lives. Generally, the observation of the rate at which the product degrades under normal room temperature requires a long time. To avoid this undesirable delay, the principles of accelerated stability studies are adopted. The International Conference on Harmonization (ICH) Guidelines titled “Stability testing of New Drug Substances and Products (QIA) describes the stability test requirements for drug registration application in the European Union, Japan and the States of America.
Applications in Pharmaceutical Formulation or Technology :
Hypromellose is widely used in oral, ophthalmic and topical pharmaceutical formulations. In oral products, HPMC is primarily used as a tablet binder (1), in film-coating,(2–7) and as a matrix for use in extended-release tablet formulations.(8–12) Concentrations between 2% and 5% w/w may be used as a binder in either wet- or dry-granulation processes. Hypromellose at concentrations between 0.45–1.0% w/w may be added as a thickening agent to vehicles for eye drops and artificial tear solutions. Hypromellose is also 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. In addition, hypromellose is used in the manufacture of capsules, as an adhesive in plastic bandages, and as a wetting agent for hard contact lenses. It is also widely used in cosmetics and food products.