31 results about "In vitro dissolution" patented technology

The application provides a high-drug-loading porous breviscapine crystal and a preparation method thereof. The crystal is prepared by a solvent diffusion method, does not contain auxiliary materials, and has high drug purity. The crystal is a highly porous, spherical, round, particle-size-controllable, large-particle-size crystal particle, and is easy to implement in an industrial scale. The process is green, and the crystal is crystallized in an aqueous solution. The solvents used can be recycled and reused. The porous breviscapine crystal prepared by the application has rapid in-vitro dissolution, improved flowability and compressibility, and is beneficial to further preparation molding.

The invention discloses an in-vitro dissolution method of a posaconazole enteric-coated tablet, which is characterized in that a Tween-80 (TWEEN-80) surfactant is added into a dissolution medium, so that the solubility of the posaconazole enteric-coated tablet in a phosphate buffer solution is remarkably improved, the phenomenon that a solution in a dissolution cup is not uniform is solved, the jump point phenomenon of a dissolution curve is eliminated, and the dissolution rate of the posaconazole enteric-coated tablet is improved. When a phosphate buffer solution added with a certain amount of surfactant is used as a dissolution medium, the accumulated dissolution amount at each time point is stable, the dissolution curve is smooth, the detection result is accurate and reliable, the repeatability and predictability of the dissolution test are remarkably improved, and a more reliable detection method is provided for the initial stage of drug research and development and quality control.

This invention belongs to the field of pharmaceutical formulation technology and discloses a baloxavir derivative tablet, its preparation method, and its application. The tablet comprises a surface-acidified passivated magnesium aluminum silicate carrier, baloxavir ester, poloxamer 188, microcrystalline cellulose, and magnesium stearate. During preparation, anhydrous citric acid is used to neutralize the basic active sites of pure magnesium aluminum silicate to construct micro-acidic channels. Subsequently, the carrier, baloxavir ester, and poloxamer 188 are mixed and heated, causing the polymer to melt, encapsulate the drug, and penetrate into the mesopores of the carrier. Finally, forced quenching treatment is performed to confine the drug in an amorphous or nanocrystalline state within the channels. This invention blocks the alkaline-catalyzed degradation pathway of baloxavir ester, maintains the high free energy state of the drug through physical spatial confinement, improves the in vitro dissolution rate, and enhances the flowability of the compressed powder.

A lacosamide pharmaceutical composition as well as a preparation method and application thereof are provided. According to the lacosamide pharmaceutical composition, lacosamide or a pharmaceutically acceptable salt thereof can be dissolved out at the same time, wherein the dissolution rate of the lacosamide pharmaceutical composition is not more than 40% within 1 hour, the dissolution rate of the lacosamide pharmaceutical composition is 20-70% within 6 hours, and the dissolution rate of the lacosamide pharmaceutical composition is not less than 65% within 24 hours. The lacosamide pharmaceutical composition has good slow release performance, the tablet size can be rapidly expanded in the in-vitro dissolution process, the expanded lacosamide pharmaceutical composition has good rigidity and elasticity and has a remarkable retention effect in the stomach, and the cumulative release rate within 24 hours can reach 80% or above.

The invention discloses a combined package of an estradiol tablet and an estradiol didrogesterone tablet and a preparation method of the combined package. The package is composed of an estradiol tablet and an estradiol didrogesterone tablet. The combined package of the estradiol tablets and the estradiol digestrol tablets comprises the estradiol tablets and the estradiol digestrol tablets which are equal in tablet number, each of the estradiol tablets and the estradiol digestrol tablets comprises a tablet core and a coating layer, the tablet cores are prepared by a high-speed shearing granulation and tabletting process, and the prepared tablets are consistent with an originally developed agent Femoston in in-vitro release behavior, and have the advantages that the estradiol tablets and the estradiol digestrol tablets are combined, so that the estradiol and the estradiol digestrol tablets can be used for preparing the estradiol digestrol tablets; and in-vivo bioequivalence can be achieved. The high-speed shearing granulation mode is used for improving the particle mixing uniformity, so that the medicine content is more uniform, the in-vitro dissolution is stable, and the inter-batch difference is reduced. According to the invention, estradiol with a particle size of less than 20 [mu] m and didrogesterone with a particle size of less than 30 [mu] m are selected, high-speed shearing granulation is carried out by using a high stirring frequency, a special water adding device with a specific opening angle is selected, and the water adding amount, the water adding time and the stirring frequency are controlled at the same time, so that the tablets with rapid dissolution, uniform content and stable quality can be obtained.

The present invention relates to an oral solid dosage form comprising ticagrelor as pharmaceutically active ingredient and at least one excipient. In particular, the present invention relates to a process for producing an immediate release ticagrelor tablet composition which is wet granulated with croscarmellose sodium or sodium starch glycolate as a disintegrant in order to produce stable in vitro dissolution profile throughout the shelf-life.

The invention relates to a furosemide tablet and a preparation method thereof.The furosemide tablet is prepared from, by weight, 25.00% of furosemide, 40%-45% of filler, 27%-33% of adhesive, 0.5%-1.5% of lubricant, 1.0%-2.0% of anti-sticking agent and 0.5%-1.5% of flow agent.The furosemide tablet is prepared by adopting the technology that purified water is directly added without preparing the adhesive; a wet granulation process is adopted, the controllability of process parameters in the production process is high, the human influence of operation of multiple process steps is reduced, the quality stability of the medicine is effectively improved, the quality of the medicine is equivalent to that of a commercially available reference preparation, and multiple dissolution curves are similar to that of the reference preparation; the in-vitro dissolution behavior similar to that of a reference preparation is shown, the quality is stable, and the dissolution behaviors among batches are consistent.

The present application relates to the technical field of pet medicine, in particular to a dissolution method of a pharmaceutical composition containing flucloronide and application thereof. The dissolution method is as follows: when the temperature of the dissolution medium is 37 DEG C + / - 0.5 DEG C, the pharmaceutical composition containing flucloronide is added, stirring is started at a speed of 80 revolutions / minute-150 revolutions / minute and timing, sampling is carried out in 1 hour-24 hours, and the dissolution medium includes 0.1-0.5 mol / L strong base and 2% w / v-4% w / v SDS. The dissolution method can be used to evaluate the in-vitro dissolution behavior of the pharmaceutical composition containing flucloronide, investigate the influence of different prescription compositions, different preparation processes and differences of raw and auxiliary materials on in-vitro dissolution, evaluate the consistency of batch quality, guide the development of generic drugs and accelerate the research and development progress of generic drugs.

The application discloses a nanometer preparation of bufonin for treating colon cancer, which has a core-shell structure, wherein the inner core is a nanocrystal composed of bufonin and a stabilizer, and the outer shell is a pH-responsive material and a pore-forming agent; the nanometer preparation of bufonin for treating colon cancer is prepared by using the stabilizer, the bufonin and the pH-responsive material; the in-vitro dissolution characteristics of the poorly soluble drug bufonin are improved by nanometerization treatment, and the dissolution characteristics are obviously improved compared with the raw drug; the pH responsiveness of the Eudragit L-100 protects the bufadienolides in the bufonin from being destroyed by the strong acidic condition of gastric juice, thereby improving the stability and effectiveness of the drug, reducing the initial release of bufalin, cinobufagin and resibufogenin in the stomach, making the drug target the intestinal site, making the three kinds of bufonin components achieve effective and rapid synergistic release in the intestinal site, increasing the utilization rate of the drug in the intestinal tract, and being beneficial to the treatment of colon cancer.

The invention belongs to the technical field of medicines, and particularly relates to an icaritin tablet and a preparation method thereof. According to the tablet prescription, the problem of in-vitro dissolution of an indissolvable drug icaritin is solved, and compared with commercially available icaritin soft capsules, the tablet has greater advantages in manufacturing cost and production efficiency compared with a soft capsule dosage form. The tablet process is easy to implement and suitable for industrial production.

The application relates to the technical field of pharmaceutical preparations, in particular to a loratadine immediate-release tablet based on a co-micronization technology and a preparation method thereof; a pharmaceutical composition comprises a co-micronization compound, the co-micronization compound comprises loratadine and a co-micronization carrier; the application discloses a loratadine immediate-release tablet based on a co-micronization technology and a preparation method thereof, the dissolution rate and stability of the loratadine are improved by adopting the co-micronization technology and a new type of excipient combination; meanwhile, the prepared loratadine immediate-release tablet also has good in-vitro dissolution performance; the loratadine immediate-release tablet prepared by the application reduces impurity growth in the production and storage processes and obviously improves the stability of the drug; the loratadine immediate-release tablet disclosed by the application does not contain lactose in the prescription, so that the side reaction of lactose intolerance can be effectively avoided.

The application belongs to the technical field of veterinary drug preparation, and particularly relates to a water-soluble florfenicol powder and a preparation method thereof. The water-soluble florfenicol powder is prepared from the following components by weight: florfenicol 20-25 parts, folium isatidis flavones 3-8 parts, a composite dispersion carrier 30-35 parts, hydroxypropyl-beta-cyclodextrin 10-15 parts, a surfactant 6-8 parts, and lactitol 3-5 parts. The water-soluble florfenicol powder prepared by adopting florfenicol and folium isatidis flavones as the effective components and cooperating with specific excipients has high in-vitro dissolution rate, can effectively improve the bioavailability and treatment effect, and has excellent storage stability, and can maintain the drug efficacy and chemical integrity even under long-time storage or specific conditions, and is not prone to degradation or deterioration.

This invention belongs to the fields of biomedicine, beauty, and personal care health technology, and specifically relates to an amorphous assembly of capryloylglycine and tranexamic acid, its preparation method, and its application. The method involves adding capryloylglycine and tranexamic acid to an alcoholic solution, rotary evaporating, and drying to obtain a co-amorphous compound; mixing a cyclodextrin compound solution with the co-amorphous compound, heating to react, and drying to obtain the product. This assembly achieves high drug loading, significantly improves apparent solubility and in vitro dissolution rate, and overcomes application bottlenecks without altering the structure and properties of the active ingredients. This invention achieves multi-pathway targeted oil control and whitening through the synergistic encapsulation of capryloylglycine and tranexamic acid, with effects superior to single components. The cyclodextrin inclusion imparts excellent stability to the system, inhibits recrystallization, and provides both solubilization and controlled release effects; the components are safe and mild, with a near-neutral pH and strong formulation compatibility; its preparation process is mild, simple to operate, has high yield, is environmentally friendly, and easily industrialized.

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a citrus flavone tablet and a preparation method thereof. Tablet cores of the citrus flavone tablets comprise 450-550 parts by weight of citrus flavone, 50-74 parts by weight of microcrystalline cellulose, 20-34 parts by weight of carboxymethyl starch sodium, 20-40 parts by weight of gelatin, 4-8 parts by weight of talcum powder and 2-6 parts by weight of magnesium stearate, the citrus flavone tablets are prepared through a one-step granulation process, a wetting process is specially added before one-step granulation, adhesion of raw material medicines in the initial stage of granulation is avoided, and the content of the raw material medicines is increased. Meanwhile, low content caused by loss of raw material medicines due to single use of a one-step granulation process is avoided. According to the present invention, the particles similar to the reference preparation are obtained by using the specific components, the specific wet granulation wetting and the one-step granulation process, the in vitro dissolution of the obtained citrus flavone tablet is similar to the reference preparation, the disintegrated particles are similar to the reference preparation, and the treatment effect is further ensured.

The invention provides a compound phosphate particle composition and a preparation method thereof. The compound phosphate granules prepared by the prescription process can effectively ensure the crystal form stability of the raw material medicines, obtain a good in-vitro dissolution effect, and meanwhile, are more favorable for preventing the aggregation phenomenon of the granules.

The invention relates to the technical field of food additive preparation, in particular to a novel curcumin self-micellization solid dispersion and a preparation method thereof.The method comprises the steps that F127 and TPGS serve as composite carriers, the composite carriers and curcumin raw material medicine are dissolved in absolute ethyl alcohol, a solvent is removed through rotary evaporation, freeze drying, grinding and sieving are conducted, and the self-micellization solid dispersion is prepared. According to the process, the solubility and the stability of the curcumin are remarkably improved, the prepared solid dispersion has the characteristics of high drug loading capacity, good physical stability and rapid in-vitro dissolution, and in a simulated digestion experiment, the release rates of the curcumin in the oral cavity and gastric juice reach 9.9% and 4.6% respectively and are far superior to those of free curcumin, so that the curcumin solid dispersion can be applied to the oral cavity and the gastric juice of the oral cavity and the gastric juice of the oral cavity and the gastric juice of the oral cavity. Through the synergistic effect of micelle wrapping and the surfactant, drug aggregation is effectively reduced, gastrointestinal adsorption and permeation are enhanced, bioavailability is greatly improved, the curcumin dispersible tablet is suitable for development of various efficient preparations such as oral administration, inhalation and percutaneous absorption, and the key problems that curcumin is poor in dissolubility and low in bioavailability are solved.

The invention discloses a piribedil sustained-release tablet and a preparation method thereof, the sustained-release tablet comprises piribedil or pharmaceutically acceptable salt, a filler, an adhesive and a lubricant, the filler is talcum powder, the adhesive is povidone, the lubricant is magnesium stearate, the lubricant is internally and externally added, and the filler is magnesium stearate. The piribedil sustained-release tablet provided by the invention is stable in quality, has consistent in-vitro dissolution with an original piribedil sustained-release tablet (an original research manufacturer: French Schwia, the trade name: Tesudoda), is simple and convenient to operate, and is beneficial to industrial production.

The invention belongs to the technical field of pharmaceutical preparations, and discloses melogabalin besylate tablets and a preparation method thereof. The melogabalin besylate tablet comprises a medicine tablet core and a coating layer, the medicine tablet core is prepared from the following raw materials in parts by weight: 4 to 10 parts of melogabalin besylate, 60 to 120 parts of a filling agent, 10 to 20 parts of a disintegrating agent, 0.5 to 1.0 part of an adsorbent and 1.0 to 2.0 parts of a lubricating agent. According to the invention, no antioxidant is added, the process adopts a direct powder tabletting technology, and the raw material medicines and the mannitol are mixed step by step in a gradient manner and assisted by a forced sieving treatment manner, so that the good mixing uniformity of the preparation is ensured; meanwhile, the risk that the preparation is unstable possibly caused by a conventional granulation process is avoided, the preparation process is simplified, and the stable quality of the tablet is also ensured. The prepared melogabalin besylate tablet has good in-vitro dissolution similarity and in-vivo bioequivalence with a reference preparation.

The present invention provides a method of treating IgA nephropathy, the method comprising: (i) identifying a pharmaceutically acceptable composition intended for treating IgA nephropathy comprising budesonide and one or more pharmaceutically acceptable excipients providing modulated release of the budesonide following administration to the gastrointestinal tract, the composition comprising budesonide and one or more pharmaceutically acceptable excipients in a standard in vitro dissolution test, the one or more excipients comprising budesonide and one or more pharmaceutically acceptable excipients comprising budesonide and one or more pharmaceutically acceptable excipients comprising budesonide and one or more pharmaceutically acceptable excipients comprising budesonide and one or more pharmaceutically acceptable excipients comprising budesonide; the following requirements are met; (a) when the dissolution medium is aqueous and has a pH of about 1.2, no more than about 10% of the budesonide is released into the dissolution medium within about 120 minutes; (b) a requirement for no more than about 10% of the budesonide to release into the dissolution medium within about 30 minutes when the dissolution medium is aqueous and has a pH of about 6.8; and (c) a requirement for release of at least about 70% of the budesonide into the dissolution medium within about 120 minutes when the dissolution medium is aqueous and has a pH of about 6.8; (ii) a step of administering said composition to a patient suffering from IgA nephropathy in need of said treatment.

The invention discloses a mometasone furoate nasal spray in-vitro dissolution detection sample as well as a pretreatment method and an in-vitro dissolution detection method thereof, and belongs to the technical field of pharmaceutical analysis. The pretreatment method of the in-vitro dissolution detection sample comprises the following steps: adding a mometasone furoate nasal spray into cellulase for enzymolysis, dispersing a mixture after enzymolysis on a microfiltration membrane, and drying to obtain the in-vitro dissolution detection sample. The invention discloses a mometasone furoate nasal spray in-vitro dissolution detection sample prepared by the pretreatment method, and an in-vitro dissolution detection method adopting the detection sample. Cellulase is added into the mometasone furoate nasal spray for enzymolysis, proper enzymolysis conditions are screened, and API particles are released from a cross-linked structure formed by the auxiliary materials, so that interference of the auxiliary materials on preparation dissolution detection is eliminated.

The invention discloses an oral solid preparation of valsartan. The oral solid preparation comprises a valsartan eutectic compound and pharmaceutically acceptable auxiliary materials, the oral solid preparation comprises tablets, capsules and granules, and the content of the active substance valsartan is 10-320 mg. The valsartan eutectic compound is prepared by forming a supramolecular compound from valsartan and a specific eutectic precursor molecule (such as nicotinamide), loading the supramolecular compound in a pore channel of a mesoporous silica nano-carrier with a high specific surface area in a confinement manner, and modifying the supramolecular compound with a surface stabilizer. According to the method, medicine crystallization is inhibited by utilizing a nano confinement effect, and the medicine exists in an amorphous or molecular-level dispersed high-energy state under the synergistic action of eutectic precursor molecules, so that the dissolution rate and oral absorption efficiency of the medicine are greatly improved. The valsartan preparation is simple in process, good in stability and suitable for industrial production, and the prepared valsartan preparation has excellent in-vitro dissolution rate and in-vivo bioavailability.

The invention relates to a pharmaceutical composition for treating diabetes and a preparation method thereof, in particular to a pharmaceutical composition containing glibenclamide and metformin. The combination of the two can complement action targets, solves the problem of failure of single-drug treatment, is especially suitable for type 2 diabetes patients with ineffective diet exercise control or insufficient single-drug curative effect, improves the medication compliance of the patients, and has the advantages of high safety and low adverse reaction incidence, and is worthy of wide popularization and application. According to the invention, the granularity of glibenclamide is controlled, and the glibenclamide is filled and then packaged by medicinal aluminum foil and polyvinyl chloride solid medicinal hard tablets, so that the dissolution rate and the stability of the medicine are optimized. The particles prepared by the method are good in flowability and easy to fill, the production efficiency is improved, and the product stability is also improved. In-vitro dissolution experiments show that the dissolution curve of the composition is consistent with that of a control preparation, and the composition has good bioavailability.

The invention relates to the technical field of pharmaceutical preparations, and discloses an application of angelica keiskei chalcone in preparation of an intervention drug for metabolism-related fatty liver diseases, and the intervention drug comprises the following raw materials: an angelica keiskei chalcone extract, a methacrylic acid-methyl methacrylate copolymer, L-arginine, nicotinamide and L-tartaric acid. The preparation process adopts a fluid phase change coprecipitation method. In the liquid preparation stage, L-arginine is utilized to realize preliminary solubilization of chalcone. Nicotinamide and chalcone construct a charge transfer complex to inhibit chemical degradation of active components in an alkaline environment. In the coprecipitation stage, L-tartaric acid constructs a spatial multidentate cross-linked network in a polymer matrix, locks the amorphous state of drug molecules, and cuts off a recrystallization channel. In the post-treatment stage, pre-cooled acid washing liquid is adopted for replacing and washing waste salt, and powder is prevented from absorbing moisture and deliquescing. The in-vitro dissolution rate, the chemical stability and the physical stability of long-term storage of the chalcone are effectively improved.

This invention discloses a nanoparticle of *Gynostemma pentaphyllum*, its preparation method, and its application. The nanoparticle is obtained by microwave calcination and quenching with rice vinegar from *Gynostemma pentaphyllum*. The microwave calcination temperature is 600-850℃, and the calcination time is 10-30 min. The particle size (D90) of the *Gynostemma pentaphyllum* nanoparticle is 100-500 nm. This invention, by combining microwave calcination and rice vinegar quenching, significantly reduces the particle size of the pulverized *Gynostemma pentaphyllum* powder, thereby greatly improving its in vitro dissolution rate. Furthermore, after modification with an alternating magnetic field, the rice vinegar quenching solution exhibits improved skin penetration efficiency and can be used as a topical preparation for detoxification, antipruritic effects, and skin repair, thus reducing resource waste and meeting the requirements of green pharmaceutical manufacturing.

The invention relates to the technical field of pharmaceutical preparations, in particular to a dapagliflozin tablet and a preparation method thereof. The dapagliflozin tablet comprises the following raw materials in parts by mass: 1-5 parts of dapagliflozin, 50-80 parts of a filler, 5-15 parts of a disintegrating agent, 1-5 parts of an adhesive, 0.5-3 parts of a stabilizer and 0.5-2 parts of a lubricant, according to the dapagliflozin tablet and the preparation method thereof, raw materials and the preparation method are improved, the in-vitro dissolution of the prepared dapagliflozin tablet can be consistent with that of an original drug, the dissolution uniformity is superior to that of the original drug, related substances of the preparation are not remarkably increased, the stability is good, the preparation process is simple, and the preparation method is suitable for industrial production. The method is suitable for large-scale low-cost production and application.

The invention belongs to the field of pharmaceutical preparations, and provides a miscarriage prevention medicine for inhibiting uterine contraction and a preparation method of the miscarriage prevention medicine. According to the invention, a double-layer tablet design of a nifedipine-nicotinamide eutectic nanocrystalline quick-release layer and a nifedipine-loaded calcium alginate sustained-release pellet sustained-release layer is adopted, and the median particle size of nifedipine in the quick-release layer is controlled to be 0.10-0.40 [mu] m through a nanocrystallization eutectic technology so as to realize quick effect; meanwhile, nifedipine in a sustained-release layer is continuously released by utilizing a calcium alginate ion cross-linked sustained-release pellet drug-loading technology, so that precise regulation and control of a two-phase release curve and collaborative optimization of interlayer bonding strength are realized, the in-vitro dissolution performance of nifedipine is improved, a release time window is prolonged, the batch-to-batch consistency is improved, and the sustained-release effect of nifedipine is improved. The problems that an existing double-layer preparation is difficult to give consideration to layering resistance and drug release differentiation, the processability and the stability of the eutectic nanocrystalline dispersoid are mutually restricted, the contradiction exists between high drug loading and release controllability of the sustained-release pellet and the like are solved, and wide clinical application value is achieved.

The invention discloses a composition containing coenzyme Q10, and a preparation method and application thereof, and belongs to the technical field of health care products. Multi-component cooperation of a formula system is combined with high-speed shearing homogenization, vacuum degassing and raw material pretreatment processes, a stabilizer, a cosolvent, a carrier and a cyclodextrin derivative are compounded for synergism, and degummed, deacidified and refined olive oil is used as an oil phase matrix, so that the dispersity and solubility of the coenzyme Q10 are improved, and the coenzyme Q10 is prepared. The in-vitro dissolution rate of the prepared composition reaches 88% or above; meanwhile, through the synergistic effect of a stabilizer system and pretreatment and degassing processes, the prepared composition can be stably stored for 6 months under the conditions that the temperature is 25 DEG C and the relative humidity is 60%, the retention rate of the coenzyme Q10 reaches 97% or above, and the coenzyme Q10 is free of discoloration, layering and precipitation after being stored for a long time and good in uniformity. In addition, the scheme is simple and convenient to operate, can meet the requirements of large-scale industrial production, and has relatively high practical application value and popularization prospect.

The invention provides a method for investigating in-vitro dissolution characteristics of butenafine hydrochloride cream by adopting an immersion pool device, and belongs to the technical field of medicines. The method comprises the following steps: loading a butenafine hydrochloride cream sample on a filter membrane, assembling with an immersion pool device, immersing into a receiving medium, respectively sampling at different times, determining the content by adopting high performance liquid chromatography, determining the accumulated release amount per unit area at each sampling time point, and calculating the content of butenafine hydrochloride. Drawing a linear regression curve of the release time of the butenafine hydrochloride cream to the cumulative release amount per unit area; the receiving medium is a phosphate buffer solution containing lauryl sodium sulfate. The butenafine hydrochloride cream in-vitro dissolution research method provided by the invention can better meet the quality evaluation requirements in drug research and development and production processes. The method not only is beneficial to improving the quality control level of the butenafine hydrochloride cream and ensuring the safety and effectiveness of the medicine, but also can provide powerful technical support for further research and development and clinical application of the medicine.

The application belongs to the technical field of animal medicine, and particularly relates to an indometacin compound preparation and a use thereof in preparing a medicine for preventing and treating chicken bursa disease. The indometacin compound preparation comprises indometacin, luffa, magnolia officinalis, and a pharmaceutically acceptable excipient. The scheme solves the problems of high infection rate, high mortality, and difficulty in prevention and treatment of chicken bursa disease, and improves the treatment effect on chicken bursa disease. Through optimization of the formula and the preparation method, the in-vitro dissolution of indometacin is improved, the stability of indometacin in the indometacin compound preparation is improved, and the impurity content of indometacin is reduced.

In certain embodiments, the present invention is directed to a solid controlled release dosage form comprising: a core comprising a first portion of an opioid analgesic dispersed in a first matrix material; and a shell encasing the core and comprising a second portion of the opioid analgesic dispersed in a second matrix material; wherein the amount of opioid analgesic released from the dosage form is proportional within 20% to elapsed time from 8 to 24 hours, as measured by an in-vitro dissolution in a USP Apparatus 1 (basket) at 100 rpm in 900 ml simulated gastric fluid without enzymes (SGF) at 37 C.