Oral extemporaneous suspensions of other drugs amiodarone, granisetron, trimethoprim, and verapamil salt prepared in methylcellulose and simple syrup MC:SS were also reported to have adequate stability [14].
Another cellulose derivative frequently used as part of a vehicle in oral extemporaneous suspensions is sodium carboxymethylcellulose. Researchers have performed stability studies for various oral suspensions of drugs with this vehicle. However, for captopril, hydralazine hydrochloride and tetracycline hydrochloride, the suspensions were reported as not having enough stability.
The problem of stability with captopril is due to its oxidative degradation, which can be solved by the addition of EDTA disodium [79]. Although, these studies are important, most of them have not evaluated the microbiological stability, an essential criterion for liquid dosage forms. There is no doubt that these drug stability results are important for providing formulations for both paediatric patients and the geriatric populations that have difficulty in swallowing capsules or tablets.
Microcrystalline cellulose is reported as an excipient diluent in oral powder and capsules extemporaneously compounded for paediatric use. Capsules and powders were prepared from commercial tablets containing 10 mg of nifedipine, which was mixed with different amounts of lactose or microcrystalline cellulose in a mortar with pestle using standard geometric dilution.
Capsules were filled by a hand-operated capsule-filling machine. The oral powders and capsules containing extemporaneously prepared nifedipine showed acceptable quality regarding content uniformity, but considerable loss of the active ingredient occurred during the compounding process for both preparations.
The authors demonstrated that oral powders of nifedipine a light sensitive drug can be replaced by capsules, which were adequately safe with either lactose monohydrate or microcrystalline cellulose as excipients for delivering a paediatric medication [81]. Recently, microcrystalline cellulose and two other common pharmaceutical excipients starch and lactose were investigated with regards to the choice of the best diluent for Gymnema sylvestre extract a plant used as an adjuvant in the treatment of diabetes mainly in China used to compound capsules.
The Gymnema sylvestre extract is available as powder that presents low flowability due to its small particle size which causes problems in the filling of the hard capsules. An evaluation of these excipients was also performed in the presence of different lubricants magnesium stearate or talc. On the other hand, starch and lactose increase the number of small particles that worsen the flowability of the powder mixture.
The foregoing suggests that microcrystalline cellulose can be an appropriate diluent in formulating similar flowable plant extracts. Carboxymethylcellulose and hydroxypropylmethylcellulose.
Some studies reveal improper use of cellulosic excipients. These capsules showed serious drug release problems in pharmaceutical tests because they did not disintegrate or dissolve at all [83]. CMC-Na and HPMC nonionic polymer were evaluated by in vitro release studies with regards to ibuprofen non-steroidal anti-inflammatory extended-release from hard gelatin capsules. Furthermore, the molecular weight of the polymer group that is directly related to the viscosity grade affects the drug release: the higher the molecular weight is, the slower the drug release is [40].
One year later, these researchers evaluated ibuprofen bioavailability healthy volunteers from hard gelatin capsules containing different grades of HPMC K and K15M and CMC-Na low, medium, high viscosity. These capsules were prepared by filling the shells with the simple mixture of the powders drug and polymer.
The study showed that different viscosities of HPMC can modify the absorption rate of ibuprofen from hard gelatin capsules, in close correlation with a previous in vitro study. On the other hand, the use of the CMC-Na with different viscosity grades did not allow for the control of the absorption rate of ibuprofen and did not correspond to in vitro results.
However, none of the polymers seemed to have any effect on the bioavailability of the ibuprofen from hard gelatin capsules [39]. Slow-release morphine opioid analgesic used for the relief of pain capsules extemporaneously prepared were investigated regarding their dissolution profile.
Three batches of capsules prepared by a pharmacist were compared with each other and with tablets acquired in the market.
The authors describe how similar slow-release profiles were found for tablets and compounded capsules, though the latter showed a faster release-rate for morphine sulphate. Despite small variations from batch to batch, the authors describe that compounded capsules showed a remarkably consistent slow-release profile in in vitro studies [34]. Another study of compounded capsules containing mg of morphine sulphate a dosage unavailable in the market reported the use of HPMC in sustained-release.
There has been considerable controversy about the advisability of this practice. Release studies, performed according to the United States Pharmacopeia USP using a dissolution apparatus of type III, showed that almost half of the morphine was released in the first hour and that the release of the remainder was not adequately sustained.
As verified in other studies, the increase of HPMC prolonged release and reduced drug release in the first hour. Considering that the medication can be taken after a meal, the agitation of the gastrointestinal tract would have increased, resulting in the reduction of the sustained release period and in a slight increase of the drug amount during the first hour after administration. In the first formulation, the capsules did not exhibit sustained-release that could be adequate for most applications.
Formulations with a greater percentage of the HPMC are preferred. Furthermore, the pelleted formulation was superior, but it may not be feasible because it is too labour-intensive [35]. Slow-release capsules of morphine sulphate 15, 60, mg and oxycodone hydrochloride 10, 80, mg were evaluated in vitro by USP dissolution apparatus II. The authors observed that the release of the active ingredients from the compounded capsules after 0.
The authors recommend that the ratio of active ingredient to polymer should remain constant regardless of the capsule size in order to achieve similar release rates, provided there is some degree of compression within the capsule shell. In vitro performance showed small intra-batch variations as well as inter-batch variations which were not statistically significant.
Thus the compounding of slow release capsules yielded reproducible formulations. However, the authors mention that clinical evaluation is needed in order to determine whether the small differences are significant [37].
A variety of drugs, especially natural bioidentical hormones, have been exploited in compounding using matrix systems since Hydrophilic matrix systems were mentioned as being successfully used in slow-release capsules. The authors report that a good response of patients in a dose-related manner was observed in response to all micronized hormones administered in slow-release capsules [36].
The polymers of HPMC were employed to prepare capsules by volumetric method for powder filling in a manual encapsulator. The extended drug release was evaluated using USP apparatus I for industrially-produced batches and for those obtained by compounding process.
Furthermore, reproducibility was observed with ten other compounded batches. HPMC was efficient in controlling the release of theophylline from the matrix of the capsules prepared by compounding. However, extended-release capsules containing mg of theophylline pellets available in the market did not show prolonged release when submitted to the same test conditions [38]. To summarize, CMC-Na does not seem to be an adequate slow-releasing agent for preparing the capsules regardless of its viscosity.
On the other hand, HPMC is a promising agent for prolonging the release of drugs, since it has been used before with success. The results suggest a relationship between degree of viscosity of HPMC and slow release ibuprofen, morphine. However, reproducibility is an important requisite, and may not be assured for all formulations. In addition, studies of therapeutic efficacy are also scarce for such compounded products.
Cellulose ester derivatives are used for enteric coatings of capsules, making them resistant to dissolution in low pH environments, such as the stomach, but allowing for their rapid disintegration in higher pH environments, such as the intestine. The efficiency of the coating is limited by the smooth and nonporous surface of the hard capsules.
Cellulose acetate phthalate. CAP and other agents formaldehyde, methacrylic acid copolymer have been used to compound delayed-release capsules of diclofenac using specific small-scale machinery or manual immersion in order to evaluate the efficiency of these enteric coating processes [32].
However, the capsules coated by machinery had a poorer visual aspect than those coated by the manual process [32]. In spite of this difference, the authors did not suggest which method was the most adequate to compound delayed-release capsules of diclofenac. A simple, quick and easily reproducible method for compounding enteric-release capsules containing diclofenac has also been described.
Results confirmed that CAP is an effective enteric coating agent in compounding practice and that the application of adequate techniques in pharmacies is important. Delayed release capsules obtained by compounding and coating with organic solutions of CAP have been evaluated for pro-drug sodium pantoprazole, a proton pump inhibitor that undergoes degradation in the acid environment of the stomach [31,84,85].
Quality control tests were performed on capsules locally acquired in compounding pharmacies. Dissolution studies for gastro-resistance evaluation were performed with granules of pantoprazole coated with CAP and encapsulated, as well as with capsules coated with CAP or other agents formaldehyde, shellac, methacrylic acid copolymer.
However, all the samples prepared by coating with CAP capsules or granules released their content in an acid environment and did not show adequate gastro-resistance [31]. These results reveal the need for suitable coating techniques for compounding gastro-resistant capsules, since CAP is admittedly an effective agent for enteric coating. Cellulose and its derivatives are very important excipients in compounded medicines.
Many compounded preparations containing such excipients have been investigated since , especially for extemporaneous use; however, a great effort is still necessary in this field in order to assure quality, safety and efficacy for several other drugs. This aspect is even more relevant when these products require specific pharmaceutical features such as delayed release and, consequently, adequate techniques for achieving drug therapy success. It points towards the need for more research into ways to properly disseminate the appropriate use of cellulose derivatives in compounding pharmacies.
For all these reasons, cellulose derivatives and their applications in compounding practice were reviewed, with an emphasis on their use in solid dosage forms with modified release. Addressing the use of the cellulose derivatives, such as cellulose acetate phthalate, can be critical in the coating of capsules by hand.
Licensee IntechOpen. Corn Starch or Potato Starch was recognized as being the ingredient in tablet formulations responsible for disintegration as early as Due to low compressibility of starch, pre-gelatinized starch was invented for using as disintegrant. Pre-gelatinized starch and MCC are two main types of classic disintegrants. In recent years, the classic disintegrnts have been gradually replaced with the newer ones called super disintegrants.
Super disintegrants can acts in lower concentrations than starch and have not detriment effect on compressibility and flowability of formulations. There are numerous drugs with unfavorable tastes.
The most prevalent unpleasant taste of the drugs is bitter taste. Unpleasant-tasting dosage forms leads to lack of patient compliance of oral drug preparations. Various tastes are feeling by taste buds on the tongue. Taste buds are onion-shaped structures containing between 50 to taste cells. Chemicals from food or oral ingested medicine are dissolved by the saliva and enter via the taste pore. They either interact with surface proteins known as taste receptors or with pore-like proteins called ion channels.
These interactions cause electrical changes within the taste cells that trigger them to send chemical signals that translate into neurotransmission to the brain. Salt and sour responses are of the ion channel type of responses, while sweet and bitter are surface protein responses.
Taste masking is an important consideration in formulation of oral dosage forms especially in the case of high dose, poorly tasting drugs. Improving the taste of liquid dosage forms is more important because of better sensitivity and faster stimulation of taste receptors by liquids in compared than solids. Taste masking in solid dosage forms can be performed by coating in the case of tablets, pellets, pills or coarse granules or micro-coating in the case of fine granules, powders or microcapsules of them by a gastro-soluble polymeric coating.
These coats can prevent from contacting of the drug with taste buds without detriment of release characteristics of the drug formulations in gastrointestinal tract.
Soluble cellulose ether derivatives are suitable for this purpose. These coats can produce additional benefits in drug formulations such as protection of the active ingredients against moisture, oxygen of the air and light due to their barrier effects.
Masking of the taste in liquid dosage forms especially in drug solutions is more sophisticated. In these cases test receptor blockers, flavoring agents and viscosity enhancers are simultaneously needed. Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution 3. Help us write another book on this subject and reach those readers.
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We are IntechOpen, the world's leading publisher of Open Access books. Built by scientists, for scientists. Our readership spans scientists, professors, researchers, librarians, and students, as well as business professionals. Downloaded: Introduction Cellulose probably is the most abundant organic compound in the world which mostly produced by plants. Cellulose Pure cellulose is available in different forms in the market with very different mechanical and pharmaceutical properties.
Cellulose ether derivatives Cellulose ethers are high molecular weight compounds produced by replacing the hydrogen atoms of hydroxyl groups in the anhydroglucose units of cellulose with alkyl or substituted alkyl groups. Cellulose ester derivatives Cellulose esters are generally water insoluble polymers with good film forming characteristics.
Application in bioadhesive and mucoadhesive drug delivery systems Bioadhesives and mucoadhesives are drug containing polymeric films with ability of adhering to biological membranes after combining with moisture or mucus compounds.
Application in pharmaceutical coating processes Solid dosage forms such as tablets, pellets, pills, beads, spherules, granules and microcapsules are often coated for different reasons such as protection of sensitive drugs from humidity, oxygen and all of inappropriate environmental conditions, protection against acidic or enzymatic degradation of drugs, odor or taste masking or making site or time specific release characteristics in pharmaceuticals to prepare various modified release drug delivery systems such as sustained release, delayed release, extended release, immediate release, pulsatile release or step-by-step release dosage forms Barzegar jalali et al.
Application in extended release ER solid dosage forms 3. In coated extended release formulations Extended release pharmaceuticals refer to dosage forms that allow a twofold or greater reduction in frequency of the drug administration in comparison with conventional dosage forms. In extended release polymeric matrices Matrices are very simple and efficient systems for controlling drug release from dosage forms.
Application in osmotic drug delivery systems In recent years, considerable attention has been focused on development of novel drug delivery systems NDDS. In SPM formulation of osmotic systems As noted earlier, each osmotic delivery system is consisted of two main components included osmotically active core and semi-permeable membrane SPM. In central core of osmotic systems Central core of an osmotic pump is generally a simple compressed tablet basically consisted of the active drug s , osmotically active agent s , hydrophilic polymer s and other commonly used ingredients such as filler, compressibility enhancer, free flowing agent and lubricant.
Application in enteric coated solid dosage form Enteric coated solid dosage forms are the main groups of delayed release drug delivery systems which designed for releasing of their drug s content in the lower parts of gastrointestinal tract such as small intestine and colon. Application as compressibility enhancers More than 80 percent of all dosage forms available or administered to man are tablets.
Application as gelling agents Gels are semisolid systems consisting of dispersions of very small particles or large molecules in an aqueous liquid vehicle rendered jellylike by the addition of a gelling agent.
Application as thickening and stabilizing agents Cellulose derivatives are extensively used for thickening of pharmaceutical solutions and disperse systems such as emulsions and suspensions Adibkia et al.
Application as fillers in solid dosage forms Cellulose and related polymers are commonly used in solid dosage forms like tablets and capsules as filler. Application as binders in granulation process Binders are the essential components of solid drug formulations made by wet granulation process. Application as disintegrating agents Solid oral dosage forms such as tablets undergo several steps before systemic absorption of the drug.
Application as taste masking agents There are numerous drugs with unfavorable tastes. More Print chapter. How to cite and reference Link to this chapter Copy to clipboard. Available from:. Over 21, IntechOpen readers like this topic Help us write another book on this subject and reach those readers Suggest a book topic Books open for submissions.
More statistics for editors and authors Login to your personal dashboard for more detailed statistics on your publications. Access personal reporting. More About Us. MCC grade. Particle size. Roller compaction. Wet granulation.
Direct compression. Superior compactability. Superior Flowability. High Density. Hydrogels are an attractive system for a myriad of applications. While most hydrogels are usually formed from synthetic materials, lignocellulosic biomass appears as a sustainable alternative for hydrogel development. The valorization of biomass, especially the non-woody biomass to meet the growing… Read More Apr 11, The objective of current research was to develop the models of dissolution prediction of tablets coated with cellulose acetate CA S or CA and cellulose acetate phthalate C-A-P blends.
Feb 8, Tableting by direct compression DC is one of the simplest and most cost-effective drug manufacturing approaches. However, most active pharmaceutical ingredients APIs and excipients lack the compression and flow properties required to meet the needs of high-speed industrial tablet presses.
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