Delivery Of Theophylline Microcapsules To The Colon Biology Essay

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This essay has been submitted by a student. This is not an example of the work written by our professional essay writers. al., "Time and pH dependent colon specific, pulsatile delivery of theophylline for nocturnal asthma." The present study demonstrated a modified chronopharmaceutical formulation based on time and pH for the delivery of theophylline microcapsules to the colon. The formulated system consisted of an insoluble hard gelatin capsule body which was filled with theophylline microcapsules and sealed with a hydrogel plug like guar gum, HPMC and sodium alginate. For overcoming the variability in gastric emptying time, the entire device was coated with an enteric polymer.

Andrea al., "Oral pulsatile delivery systems based on swellable hydrophilic polymers" In this study, the various hydrophilic polymers used in the different pulsatile release formulations like reservoir, capsular and osmotic formulations were studied. The water swellable polymers especially polysaccharidic compounds have been exploited to the greatest extend in the delayed release formulations. These hydrophilic polymers have shown to successfully provide a lag phase required, by undergoing swelling, dissolution or erosion processs and thus enabling its use in chronotherapeutic approaches.

Mohammad al., "Propranolol hydrochloride osmotic capsule with controlled onset of release" Propranolol hydrochloride osmotic capsule was formulated and evaluated. The system consisted of an hard gelatin capsule coated with ethyl cellulose with or without castor oil and was filled with propranolol hydrochloride along with sorbitol which functioned as an osmotic agent. Beeswax plug was used for sealing the capsule body. The various factors like membrane thickness, plug thickness, concentration of cellulose acetate and castor oil was also studied and the system was found to be useful for chronotherapeutic purposes.

Sindhu al., "Development of modified pulsincap drug delivery system of metronidazole for drug targeting" The formulated design consisted of a formaldehyde treated hard gelatin capsule containing the metronidazole pellets and plugged with polymers like guar gum, HPMC-10K, carboxymethylcellulose sodium and sodium alginate at different concentrations. The prepared capsules were further coated with an enteric polymer and a lag time of about 5 hrs was obtained.

Usha Yogendra al., "Chronotherapeutic drug delivery for early morning surge in blood pressure: A programmable delivery system" The study involved the formulation of a system which contained a swellable polymer like xanthan gum, sodium alginate, L-HPC or poly ethylene oxide along with the drug (valsartan) tablet and an erodible tablet of L-HPC or guar gum in a pre coated capsule. The drug release was influenced by the type and amount of polymers and also the erodible tablet. Everted rat intestinal segment was used for the dissolution - absorption study and it indicated a successful delay in absorption of the drug.

Hong-Liang al., "Release characteristics and in vitro-in vivo correlation of pulsatile pattern for a pulsatile drug delivery system activated by membrane rupture via osmotic pressure and swelling" The performed study demonstrated that for a Pulsatile drug delivery system based on the principle of membrane rupture, the core and the coating formulation influences the release profile. The thickness, hydrophilicity and the osmotic effect of the semi permeable membrane and the swellability of the excipients determined the lag time of the system. Also the addition of a hydrophilic plasticizer showed a decrease in the lag time.

Akhgari, F. al., "Combination of time-dependent and pH-dependent polymethacrylates as a single coating formulation for colonic delivery of indomethacin pellets" In this study a combination of two pH dependent polymers (Eudragit S100 and Eudragit L100) and a time dependent polymer (Eudragit RS) was used for designing a formulation for the delivery of indomethacin pellets to the colon. The lag time of the system was affected by the coating level and its optimum was found to be 10%.

T.Y. al., "An investigation of pulsatile release tablets with ethylcellulose and Eudragit L as film coating materials and cross-linked polyvinylpyrrolidone in the core tablets" In the present study, the system formulated for the pulsatile delivery of diltiazem hydrochloride consisted of a coating of ethyl cellulose and Eudragit L and cross linked poly vinyl pyrrolidone was employed as the swelling agent. The PH of above 6 caused Eudragit L to dissolve and created pores in the coating through which water permeated and caused the expansion of the swelling agent which resulted in the burst release of the drug. The in vivo study showed good correlation with the in vitro data.

Ina al., "Pulsatile drug release from an insoluble drug body controlled by an erodible plug" The formulated system consists of an impermeable capsule body housing the drug and an erodible plug which is prepared by either direct compression or by the congealing of a meltable plug material. With increasing molecular weight of the hydrophilic plug material and decreasing concentration of the filler, the erosion time increased. Congealable lipid plugs and surfactants decreased the erosion time. The effect of various excipients like effervescent agents on the rapid release of drug was also demonstrated.

Pedro R. al., "Influence of adjuvants on the in vitro dissolution of hydrochlorothiazide from hard gelatin capsules" The aim of the study was to determine the influence of various excipients like fillers, lubricants and surfactants on the dissolution of hydrochlorothiazide from hard gelatin capsules. The formulations with no surfactant showed the lowest dissolution profile. The greatest effect on the dissolution profile was due to lubricants and then by the filler. Hydrophobic lubricants like magnesium stearate showed lesser dissolution efficiency than aerosil. Though both micro crystalline cellulose and lactose are hydrophobic, because of the water incorporation property of the micro crystalline cellulose, it showed better dissolution efficiency than lactose.

Rebecca L. al., "The utility of cyclodextrins for enhancing oral bioavailability" The ability of β- cyclodextrin to enhance the oral bioavailability of drugs was examined in this study. The complexation of the drug with β- cyclodextrin improved the bioavailability better than the physical mixture. The dissolution and absorption of the inclusion complex was found to be related to the physical and chemical property of the drug, β- cyclodextrin and also the dosage form. al., "Different HPMC viscosity grades as coating agents for an oral time and/or site-controlled delivery system: a study on process parameters and in vitro performances" The study involved the development and optimization of a formulation devised to release drug after a lag time or to deliver the drug to the colon using different grades oh HPMC. Methocel® E50 was found to be the better hydrophilic polymer as it was least affected by the concentration of the coating solution, medium ph and ionic strength.

Julie al., "The tolerability of multiple oral doses of Pulsincap TM capsules in healthy volunteers" The peformed study was double-blind and had a placebo-controlled parallel group. Twelve healthy subjects were involved in the study of which eight subjects were given Pulsincap TM capsules and four subjects were given a matching placebo capsule. The eight subjects who received the Pulsincap TM capsules showed no evidence of adverse events and the formulation was well tolerated. The results of the study showed that Pulsincap TM capsules can be formulated for the delivery of therapeutic agents.

Howard N.E. al., "Evaluation of Pulsincapâ„¢ to provide regional delivery of dofetilide to the human GI tract" The study was designed to formulate a delivery system to release dofetilide, a well absorbed drug following a 5hr delay or to target its release to the lower gastrointestinal tract. Dofetilide showed a reduced bioavailability when delivered from the Pulsincapâ„¢ formulations. The site of drug release and in vitro in vivo correlation was determined from the scintigraphic analysis.

T. al., "A pulsatile drug delivery system based on rupturable

coated hard gelatin capsules" In the present study, the system formulated consisted of a hard gelatin capsule which was coated first with a swelling layer, and then with an outer insoluble water-permeable polymer. The lag time increased with increasing coating thickness and decreased on the addition of a hydrophilic pore former. The swelling caused due to the water ingress through the outer polymer resulted in the rupturing of the coating and there by the drug release. The extent of medium uptake was almost the same for the different coating levels. The addition of the hydrophobic particulate material to the coating resulted in a reduced lag time.

Jason T. Mc al., "The effect of wet granulation on the erosion behavior of an HPMC-lactose tablet, used as rate controlling component in a pulsatile drug delivery capsule formulation" In the study it was demonstrated that the HPMC tablets prepared by wet granulation showed longer lag times compared to those prepared by direct compression. This was more prominent at low concentrations of HPMC. Microwave dielectric analysis was used for determining the degree of polymer spreading in the aqueous system. al., "Evaluation of the swelling, hydration and rupturing properties of the swelling layer of a rupturable pulsatile drug delivery system" The study exhibited a linear correlation between the water uptake and the swelling layer. The ionic strength and the pH of the medium was shown to influence the swelling behavior of Ac-Di-Solw which was due to the acidic nature of the polymer and the competition for free water. The analysis of the time dependent swelling force data confirmed that the penetration rate of the medium controlled the diffusion controlled swelling force development.

Gordon L. al., "Pharmacokinetics of an immediate release, a controlled release and a two pulse dosage form in dogs" In the present study, for each dosage form the pharmacokinetic parameters were determined. On comparing the plasma time curves, it was found that there was a significant difference in the drug plasma levels for each dosage form. For each dose between 1 - 1.75 and 2.5 - 3.5 hr, two defined Cmax values were obtained.

Roland al., "Floating or pulsatile drug delivery systems based on coated effervescent cores" In the present study it was demonstrated that the time of floatation depended on factors like the concentration of the effervescent agent, the type of filler, hardness of the core tablet and the thickness and composition of the polymer like the type of polymer and plasticizer used. In order to facilitate a rapid drug release after the lag phase, a quick release core was formulated. The lag time increased with increasing coating level and core hardness.

Joseph al., "Responsive polymeric delivery systems" In the present study, the fundamental principles of the self regulated delivery systems and the externally regulated delivery systems were studied. According to the physiological need these systems are capable of adjusting the release rate of the drugs. The advantages and disadvantages of the different approaches according to the different clinical conditions like diabetes were also evaluated.

Ross al., "Chronopharmaceutical drug delivery from a pulsatile capsule device based on programmable erosion" The present study involved the development of a pulsatile drug delivery device which consisted of an insoluble capsule body containing the drug formulation (propranoloI hydrochloride) and sealed with an erodible tabet. With the increasing concentration of dibasic calcium phosphate ( insoluble excipient) and HPMC( gel-forming excipient), the lag time was also found to increase. The time release was influenced by the composition and weight of the erodible tablet. The formulated system can be used for the development of a chronopharmaceutical delivery system with a lag time ranging from 2-12 hrs by manipulating the erodible tablet formulation.

Björn al., "Circadian rhythms and drug delivery" The functions of the body are found to follow circadian rhythm eg. Blood pressure, heart rate, blood flow, pulmonary, hepatic and renal functions. Therefore the onset of diseases and also their symptoms show a variation within the 24 hrs of a day. The pharmacokinetics and pharmaco-dynamics of the different drugs like anti-asthmatics, H-2 blockers and cardiovascular drugs also show daily variation. So it can be summarized that while evaluating a drug delivery system, the biological rhythm of the body functions has to be taken into account.

Hermida al., "Administration-time-dependent effects of antihypertensive treatment on the circadian pattern of blood pressure" The study was performed to develop a methodology for the treatment of hypertension taking into account the circadian blood pressure pattern. The difference in the time of administration of a drug has shown a difference in its anti-hypertensive action. Nifedipine gastrointestinal therapeutic system showed better anti-hypertensive action and a significant reduction in blood pressure when administered at bedtime than when compared to the early morning administration.

Nayak al., "Chronotherapeutic drug delivery for early morning surge in blood pressure: a programmable delivery system" The objective of the study was to formulate a pulsatile delivery system for valsartan. . The formulated system contained swellable polymer like L-HPC, polyethylene oxide, xanthan gum or sodium alginate along with the drug tablet and an erodible tablet (L-HPC or guar gum)enclosed in a pre-coated capsule. The various formulation parameters were investigated. The drug release was influenced by the type and amount of polymers and the erodible tablets. A delayed absorption of drug was observed from the continuous dissolution-absorption study performed using everted rat intestine.

Ishino R et al., developed a dry-coated tablet with a pulsatile drug release profile to achieve a time-controlled and site specific delivery of the drug to the gastrointestinal tract. The formulated delivery system consisted of a permeability controlled outer shell with a swellable core tablet. The drug was released rapidly after a certain period of lag time because of the time-controlled disintegration mechanism. Water penetration rate was tested with different model disks of outer shell, which consisted of hydrogenated castor oil and poly ethylene glycol 6000. The study results showed that the lag time of the system could be controlled by changing the thickness and composition of the outer shell. On comparing the different disintegrants, carboxy methyl cellulose calcium was found to be the better disintegrant which can be used for the core tablet. Various pulsatile release tablets with different lag times were designed for the drug isoniazide based on the fundamental studies and the in vitro dissolution study showed a typical pulsatile drug release.

Teruo Okano et al., has discussed the different types of drug delivery systems employing hydrogels which posses pulsatile drug delivery characteristics. It has been observed that many vital functions of the human body is regulated by the transient or pulsed release of bioactive substances so it is important to deliver certain drugs a pulsed manner so as to mimic the functions of the body and minimize side effects. The present study has mainly focused on the thermally responsive poly(N-isopropylacrylamide) and its hydrogel derivatives. The article also describes about the modified alginate gel beads development which has a characteristic pulsatile delivery.

Bin Li, JiaBi Zhu et al., developed a pulsatile drug delivery system which delivers drug three times daily. The tablets in capsule system consisted of an impermeable capsule body with two multi-layered tablets and a water-soluble cap. Hydroxy-propyl methyl cellulose and sodium alginate was used as the modulating barrier material. The weight and the type of material of the modulating barrier significantly affected the lag time. The lag time was controlled between two pulsatile releases by adjusting the ratio of lactose and sodium alginate. The ratio and lag time showed a linear relationship. The study also demonstrated that by the addition of a separating layer between the third and the modulating barrier layer, the release rate of the second pulsatile dose can be improved. It was also found that the use of lactose as bulking agent improved the drug release rate.

Bin Li, JiaBi Zhu et al., developed a pulsatile drug delivery system which delivers drug three times daily. The tablets in capsule system consisted of an impermeable capsule body with two multi-layered tablets and a water-soluble cap. Hydroxy-propyl methyl cellulose and sodium alginate was used as the modulating barrier material. The weight and the type of material of the modulating barrier significantly affected the lag time. The lag time was controlled between two pulsatile releases by adjusting the ratio of lactose and sodium alginate. The ratio and lag time showed a linear relationship. The study also demonstrated that by the addition of a separating layer between the third and the modulating barrier layer, the release rate of the second pulsatile dose can be improved. It was also found that the use of lactose as bulking agent improved the drug release rate.

Viral Shah et al., developed a multiple unit based pulsatile delivery system for the treatment of asthma based on chronopharmaceutics using the drug salbutamol sulphate which also exhibits advantages like less side effects and first pass metabolism. The system consisted of an immediate release layer and a pulsatile release layer. The drug was loaded on to the non-pareil seeds using PVP-K-30(2%) as the binder in a conventional coating pan. It was coated with different concentrations of coating agent that is cellulose acetate phthalate and a constant concentration of ethyl cellulose. The study showed that the concentration of 4% CAP and 2% ethyl cellulose showed a successful pulsatile release.

Srikanth MV et al., has discussed the different types and approaches involved in the development of pulsatile delivery system. Pulsatile delivery system has been classified into different type mainly based on the mechanism involved. The different systems discussed are time dependent systems, stimuli induced systems, external stimuli induced systems and pulsatile release systems for vaccines and hormones. In the time controlled systems the drug release is controlled by the delivery system, in stimuli induced pulsatile system the release is controlled by different stimuli such as pH, enzymes present in the intestinal tract or the delivery system and external stimuli like magnetism, ultrasound, electrical effect or irradiation.




Chemical name : 6-Chloro-3,4-dihydro-2H-1,2,4- benzothiadiazine-7-sulfonamide 1,1-dioxide

Molecular formulae : C7H8ClN3O4S2

Molecular weight : 297.73

Description : white or almost white, crystalline powder, odourless

Solubility : soluble in acetone; sparingly soluble in ethanol(95%); very slightly soluble in water. Dissolves in dilute solutions of alkali hydroxide.

Ultraviolet spectrum : 273nm

Category : Diuretic

Dose : 12.5 to 100mg

Dosage form : capsules, tablets, oral solution


Hydrochlorothiazide, belonging to the thiazide class of diuretics, acts by blocking the reabsorption of sodium and chloride ions, and it thereby increasing the quantity of sodium traversing through the distal tubule of the nephron and thus increasing the volume of water excreted.


The three mechanisms proposed for the acute antihypertensive effects of thiazides are reduction in blood volume and cardiac output, natriuretic effect and a direct vasodilatory effect. The plasma volume returns toward normal with its chronic administration but peripheral vascular resistance is decreased.


Bioavailability : 65-75%

Protein binding : 40-60%

Metabolism : does not undergo significant metabolism

(>95% excreted unchanged in urine)

Excretion : Primarily excreted unchanged in urine

Half-life : 6 to 10 hours / 2.5 ± 0.2 hrs

Routes : Oral


Synonyms : Cellacefate, Cellulose acetate phthalate, cellulose acetate hydrogen phthalate, Aquacoat cPD

Chemical name : Cellulose acetate 1,2-benzenedicarboxylate

Functional category : Coating agent

Description : White, free-flowing powder or colorless flakes; odourless or with a faint odour of acetic acid; hygroscopic.

Solubility : Freely soluble in acetone; soluble in diethylene glycol and in dioxan; practically insoluble in water, in ethanol (95%), in toluene and in chlorinated and non-chlorinated aliphatic hydrocarbons. It dissolves in dilute solutions of alkalis.

Melting point : 192áµ’C

Density (bulk) : 0.260 g/cm3

Density (tapped) : 0.266 g/cm3

Use : used as an enteric film coating material or as a matrix binder for tablets and capsules.


Synomyms : Aquacoat ECD; Aqualon; Ashacel; E462; Ethocel; Ethylcellulosum; Surelease.

Chemical name : Cellulose ethyl ether

Functional Category : Coating agent; flavoring agent; tablet binder; tablet filler; Viscosity increasing agent

Description : Ethyl cellulose is a tasteless, free-flowing, white to light tan colored powder.

Solubility : practically insoluble in glycerin, propylene glycol and water; freely soluble in chloroform, methyl acetate and tetrahydrofuran, and in mixtures of aromatic hydrocarbons with ethanol (95%).

Density (bulk) : 0.4 g/cm3

Use : Hydrophobic coating agent for tablets and granules; Ethyl cellulose coatings are used to modify the release of a drug, to mask an unpleasant taste, or to improve the stability of a formulation


Synonym : Bleached wax; cera alba

Chemical Name : White beeswax

Functional Category : Controlled-release agent; stabilizing agent; stiffening agent.

Description : Yellowish-white pieces or plates, translucent when thin, with a fine grained, matt, non-crystalline fracture; becomes soft and pliable when warmed by hand. Odour, faint and characteristic.

Solubility : Partially soluble in hot ethanol (90%) and in ether; practically insoluble in water; completely soluble in volatile and fixed oils.

Melting range : 60-67áµ’C

Density : 0.95-0.96 g/cm3

Use : Used to increase the consistency of creams and ointments, and to stabilize water-in-oil emulsions. White wax is used to polish sugar coated tablets and to adjust the melting point of suppositories.


Molecular Formula : C56H108O30

Molecular Weight : 3912.39

Description : White to off-white powder

Solubility : Swells in cold water, insoluble in hot water, soluble in most organic solvents.

Melting point : 56.2áµ’C

Density : 1.39 g/cm3

Chemical properties : HPMC is cellulose ether, derived from alkali treated cellulose that is reacted with methyl chloride and propylene.

Uses : Used as an enteric film coating material or a matrix binder in solid dosage forms. Used as a viscosity control agent, gelling agent, film former, stabilizer, dispersant, lubricant, binder, emulsifying agent and suspending agent. End applications include adhesives and glues, agriculture, building materials, personal care products, detergents and surfactants, paints, printing inks and coatings, pharmaceuticals, food products, polymerization and textiles.