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1.
Acta Pharmaceutica Sinica ; (12): 1312-1321, 2022.
Article in Chinese | WPRIM | ID: wpr-924761

ABSTRACT

The amorphous solid dispersion is one of the most effective formulation approaches to enhance the oral bioavailability of poorly water-soluble drugs. However, the amorphous drugs tend to crystallize during storage or dissolution due to inadequate formulations, preparation techniques, storage and dissolution conditions, thus negating their advantages. Meanwhile, it is often difficult to establish in vitro-in vivo correlation for amorphous solid dispersions owing to the difference between dissolution media and physiological environments and between the apparent concentration and membrane transport flux, the dynamic process of the in vivo absorption, which put great challenges to the development of amorphous solid dispersion products. This review covers the recent progress on the mechanistic study of the in vitro dissolution and in vivo absorption of amorphous solid dispersions, aiming to provide guidance for the formulation development of poorly soluble drugs.

2.
Acta Pharmaceutica Sinica ; (12): 1486-1494, 2022.
Article in Chinese | WPRIM | ID: wpr-924736

ABSTRACT

Solid dispersion, a dispersion system in which drug molecules are highly dispersed in carrier materials, has been commonly used to improve the solubility and dissolution rate of poorly soluble drugs. The miscibility between drug and carrier is crucial to improve the dissolution performance and stability of solid dispersion. Therefore, the selection of carrier types and the optimization of drug loading are very important. In the current study, the solubility parameter method and Flory-Huggins theory were used to predict the miscibility between olaparib (OLP) and different carriers (VA64, Soluplus, Plasdone S630 and Kollidon K29/32). Besides, the carrier material with good miscibility was experimentally screened by differential scanning calorimetry (DSC). The optimum of drug-carrier ratio was further performed based on the miscibility phase diagram of drug and carrier. Theoretical calculation and experimental evaluation showed that the miscibility of OLP and VA64 was the best, and the drug loading of 30% could meet the requirements of large drug loading and physical stability. Polarizing light microscope, X-ray powder diffraction, DSC and laser confocal Raman spectroscopy exhibited that OLP was amorphous form in the solid dispersion system. Powder dissolution test demonstrated that the solid dispersion showed significantly enhanced dissolution rate in comparison to crystalline OLP. In this study, theoretical calculation and experimental evaluation were used to screen the types of carriers and optimize the drug loading, which provides an efficient strategy for the selection of carrier and the amount used in solid dispersion.

3.
Braz. J. Pharm. Sci. (Online) ; 58: e18553, 2022. tab, graf
Article in English | LILACS | ID: biblio-1360166

ABSTRACT

Abstract The aqueous solubility of cefixime trihydrate (a water insoluble drug) using different hydrotropic agents was determined and solid dispersions of cefixime trihydrate were prepared by hydrotropic solubilization technique. The drugs content were determined. The aqueous solubility of v was increased many fold in presence of sodium acetate trihydrate as hydrotropic agent. This hydrotropic agent was used to prepare solid dispersion of cefixime trihydrate. Cefixime trihydrate and sodium acetate trihydrate were accurately weighed and taken in a 200 mL beaker. Distilled water 10-15 mL was taken to dissolve hydrotropic agent using heat (48-50 °C). The drug was then added to it and magnetically stirred till whole mass get viscous. The solid dispersions of cefixime trihydrate were characterized by XRD, DSC and IR studies. DSC thermogram, XRD and Infra-Red spectra were studied. Solid dispersions, thus prepared, showed faster release of the drug as compared to pure drug and physical mixture.


Subject(s)
Solubility/drug effects , Pharmaceutical Preparations/analysis , Methods , Water , Sodium Acetate/administration & dosage , Cefixime/adverse effects
4.
Braz. J. Pharm. Sci. (Online) ; 58: e18946, 2022. tab, graf
Article in English | LILACS | ID: biblio-1364411

ABSTRACT

Abstract To investigate structure-property relationship of polymer-based curcumin solid dispersion (SD), three acrylic polymers were used to formulate curcumin SD by solvent evaporation method. Curcumin Eudragit EPO SD (cur@EPO), curcumin Eudragit RS PO SD (cur@RSPO) and curcumin Eudragit RL PO SD (cur@RLPO) showed deep red, golden orange and reddish orange color, respectively. Cur@RSPO entrapped 15.42 wt% of curcumin followed by cur@RL PO and cur@EPO. FTIR spectra indicated that in cur@EPO, curcumin may transfer hydrogen to the dimethylaminoethyl methacrylate group and thus change its color to red. In contrast, curcumin may form hydrogen bonding with Eudragit RS PO and Eudragit RL. Curcumin exists in amorphous state in three SDs as proved by differential scanning calorimetry and X-Ray diffraction measurement. In vitro digestion presented that lower pH value in simulated gastric fluid (SGF) stimulates the curcumin release from cur@EPO while permeability influences the release profile in other two SDs. When in simulated intestinal fluid (SIF), first order release model governs the release behaviors of all three SDs which showed sustained release pattern. Our results are helpful to elucidate how structure of polymer may impact on the major properties of curcumin contained SD and will be promising to broaden its therapeutic applications.


Subject(s)
Polymers , Curcumin/analysis , Methods , Solvents/administration & dosage , X-Ray Diffraction/instrumentation , In Vitro Techniques/methods , Calorimetry, Differential Scanning/methods , Evaporation/classification , Spectroscopy, Fourier Transform Infrared , Color , Citrus sinensis/classification , Hydrogen-Ion Concentration
5.
China Pharmacy ; (12): 1862-1867, 2021.
Article in Chinese | WPRIM | ID: wpr-886280

ABSTRACT

OBJECTIVE:To prepare Azelnidipine enteric solid dispersion and evaluate its quality. METHODS :Azelnidipine enteric solid dispersion was prepared by solvent method. Taking cumulative dissolution rate as the index ,single factor test was used to optimize carrier material type and its ratio. The quality of the product was evaluated by DSC ,XRD and FTIR ,and its stability was investigated. RESULTS :After azelnidipine and carrier material of Eudragit L 100-55 acrylic resin were prepared to enteric solid dispersion at a ratio of 1∶5(m/m),its dissolution rate was significantly improved. DSC ,XRD and FTIR method had all verified the crystal form of azelnidipine changed and it existed in amorphous form. The results of stability test showed that Azelnidipine enteric solid dispersion was stable under high temperature (60 ℃),high humidity (75%)and strong light [ (4 500±500)lx] for 10 days. CONCLUSIONS :Azelnidipine enteric solid dispersion by solvent method with Eudragit L 100-55 acrylic resin as carrier can eliminate the influence of crystal form ,improve dissolution and has good stability.

6.
Article in Chinese | WPRIM | ID: wpr-876143

ABSTRACT

@#As a typical BCS Ⅱ drug, felodipine exhibits low solubility and high permeability. We herein investigated the effects of different solubilization strategies on the oral absorption of felodipine. Firstly felodipine tablets based on 200 μm, 150 μm and 25 μm particle size of bulk drug were prepared. Meanwhile, felodipine solid dispersion and felodipine nanosuspension with average particle size of (168.90 ± 6.22) nm, PDI of 0.11 ± 0.06 were prepared. The absorption rate, apparent permeability coefficient (Papp), absorption quality in duodenum, jejunum, ileum and colon of rats and in vivo pharmacokinetics of the above different felodipine preparations were investigated. The results of rat single-pass intestinal perfusion showed that the absorption of felodipine preparations in duodenum, jejunum and ileum was better than in colon. Felodipine had a wide absorption window in the small intestine, with the best absorption site in the small intestine. Papp of different felodipine preparations was greater than 2.0 × 10-5 cm/s. Thus, the low solubility was the main factor limiting the absorption. In vivo pharmacokinetic experiments demonstrated the solubilization strategies significantly improved the bioavailability. The bioavailabilities of felodipine tablets with particle sizes of 150 and 25 μm, as well as nanosuspension, and solid dispersion were 138.75%, 173.01%, 208.65% and 314.53% that of the tablets with particle size of 200 μm, respectively. Solubilization strategies can significantly improve the gastrointestinal absorption rate and absorption quality of felodipine, and thus improve its bioavailability, which provides some reference for the research on the improvement of oral absorption of BCS II drugs.

7.
Braz. J. Pharm. Sci. (Online) ; 57: e18910, 2021. tab, graf
Article in English | LILACS | ID: biblio-1345454

ABSTRACT

Chemotherapy induced nausea and vomiting (CINV) is an issue, which usually occurs in cancer patient. Despite high bioavailability of oral and intravenous administration, these have some drawbacks. The oral route causes hepatic first pass metabolism and intravenous route is invasive in nature. Hence, antiemetic drug by means of transdermal route is necessary to administer in such cases. The aim of the present investigation is to develop suitable Transdermal Therapeutic System (TTS) with an objective to enhance solubility and skin permeability properties of metoclopramide base. Preformulation study begins with an approach to enhance solubility of 40 metoclopramide base by solid dispersion technique. transdermal films were prepared with 41 the solid dispersion as well as with pure drug. Phase solubility study at various temperatures reveals binding constants (Ka, 95-350 M-1 for PVP K30; 56-81 M-1 for HPßCD). Spontaneity of solubilization was justified by AL type linear profiles. The films showed satisfactory diffusion (%), permeation rate and flux after 8 h study. The transdermal patches as prepared were analyzed under FTIR, DSC and SEM. Both solubility and permeability rate in this investigation have been enhanced. So, it can be affirmed that this route would effectively enhance bioavailability


Subject(s)
Solubility , Metoclopramide/antagonists & inhibitors , Patients/classification , Pharmaceutical Preparations/administration & dosage , Biological Availability , Spectroscopy, Fourier Transform Infrared , Diffusion/drug effects , Drug Therapy , Administration, Intravenous/instrumentation , Motion Pictures , Neoplasms/pathology
8.
Article | IMSEAR | ID: sea-206335

ABSTRACT

The present research is aimed at enhancing solubility and drug dissolution of clopidogrel (CPG) used as oral antiplatelet agent by employing solid dispersion (SD) technique. Total 40 SDs formulated with drug: polymers (pluronic F127, poloxamer 407, labrafil PG, PEG 6000, gelucire 50/13), in varying ratios (1:0.5, 1:1, 1:2, 1:3, 1:4) of which CPG1 to CPG20 and CPG21 to CPG40 prepared by adopting solvent evaporation method fusion (melt) method respectively. The formulation CPG40 containing pluronic F127 as polymer showed highest solubility of 6.57±0.04 mg/ml) that is 45 folds than pure drug. Similar results reflected in the dissolution studies where CPG40 containing CPG: pluronic F127 in 1:4 ratio showed maximum % drug content, % practical yield and drug dissolution of 99.14% in 60 minutes when compared with other formulations and pure drug (32.76%) obtained by fusion melt method. From FTIR studies the optimized formulation CPG40 showed the compatibility between drug and polymers. XRD and SEM studies showed CPG40 exists in amorphous form that fetched in better drug release from the SD formulation in comparison to pure drug.

9.
Article | IMSEAR | ID: sea-210604

ABSTRACT

Diacerein (Diacetylrhein, DCN) is anthraquinone derivatives used in the curing of osteoarthritis, but its usage isrestricted due to its very poor solubility and wettability which result in bioavailability variation. The objective ofthis work was to design fast dissolving tablets (FDTs) of DCN solid dispersion. Solid dispersions (SDs) and physicalmixtures (PMs) were prepared with PEG4000, Polyvinylpyrolidone K25 (PVPK25), and Sorbitol. SD formationincreased the dissolution rate of DCN compared to PM; this demonstrates that the improvement of dissolution ratewith SD can be due to physical change in drug crystal which was confirmed by thermal analysis. SD with Sorbitol wasselected for the preparations of FDTs. Seven formulations were prepared by direct compression method using differentconcentrations of crospovidone (CP) as superdisintegrant and camphor as subliming agent. Pre- and post-compressionevaluation were carried for powder blend and the prepared FDTs, respectively. F7 (composed of 120 mg CP, 45 mgcamphor, 200 mg SD containing 50 mg DCN, 7.5 mg aspartame, 2.5 mg menthol, 2.5 mg Magnesium stearate, and22.5 mg lactose) showed the shortest disintegration time and the highest dissolution rate and it was selected for furtherinvestigation. Kinetic studies of the in vitro release results showed that F7 followed first-order kinetics. Stabilitystudies conducted for formula F7 showed good stability upon storage at 30oC/75% RH and 40oC/75% RH for 12 weeks.

10.
Int J Pharm Pharm Sci ; 2020 Apr; 12(4): 37-42
Article | IMSEAR | ID: sea-206079

ABSTRACT

Objective: The present study aimed to improve the rate of dissolution of furosemide by solid dispersion technique. Methods: Solid dispersion of furosemide was prepared by using hydrogel isolated from the seeds of Lepidium sativum as a novel carrier by the solvent evaporation method. Solid dispersion was evaluated to study the improvement in the rate of dissolution. Molecular dispersion of furosemide in the novel carrier was studied by DSC and FTIR studies. Solid dispersion was filled in capsules after stability studies and the formulation was optimized by adopting factorial design. Results: Solid dispersion of furosemide exhibited dissolution improvement from 13.54 % (plain furosemide) to 69.12% (solid dispersion) in the first 60 min. Improvement in dissolution efficiency was found to be retained after stability studies. Capsules were filled with the formulation of solid dispersion using two different grades of lactose-α lactose monohydrate and anhydrous lactose and were found stable after stabilization studies. Conclusion: The dissolution improvement of furosemide was attributed to its molecular dispersion in the novel carrier selected for this study. The recrystallization of furosemide was prevented due to intermolecular interaction between the novel carrier and furosemide. This was confirmed by FTIR. Evaluation of the dissolution data of factorial batches was analyzed by ANOVA. Analysis of the data revealed that selected levels of α lactose monohydrate and anhydrous lactose would be useful to navigate design space.

11.
Article in Chinese | WPRIM | ID: wpr-825622

ABSTRACT

Objective To evaluate the effects of different solubilizing techniques on the in vitro dissolution and in vivo pharmacokinetics of Sirolimus (SRL). Methods Solid dispersions (SD), inclusion complex (IC), self-micro emulsifying drug delivery system (SMEDDS) and nano-structured lipid carrier (NLC) were selected as the solubilization technology for SRL. SRL-SMEDDS and SRL-NLC have obtained the optimal prescription in the previous studies. Additionally, the formulation process of SRL-SD and SRL-IC was screened by using inclusion rate and dissolution profiles as indicators. 0.4% SDS, water and buffer solutions with pH 1.2, 4.5, 6.8, 7.4 were used as dissolution media. The dissolution profile of the commercially available formulation Rapamune® and the lab-made solubilized preparations were investigated. The in vivo absorption of the above preparations was examined using a pharmacokinetic test in Beagle dogs. Results In 0.4% SDS, the dissolution of each preparation exceeded 80% in 2 h. In the medium of pH 1.2, the dissolution of SRL-SD could not be measured while the dissolution of IC, SMEDDS and NLC increased first and then decreased. In other media, the dissolution of the SRL was reduced. The SRL-IC showed the best dissolution without a significant decrease. The relative bioavailability of APIs, SRL-SD, SRL-IC, SRL-NLC and SRL-SMEDDS were 9.1%, 18.7%, 33.2%, 78.0%, and 97.6% respectively in vivo pharmacokinetic tests. Conclusion SD, SMEDDS, NLC, and IC can improve the in vitro dissolution and in vivo absorption of SRL. Among them, SMEDDS has the most significant improvement in the bioavailability of SRL.

12.
Chinese Pharmaceutical Journal ; (24): 169-176, 2020.
Article in Chinese | WPRIM | ID: wpr-857780

ABSTRACT

The low aqueous solubility is the main reason that for most pharmacological active ingredients are challengeable to develop into oral solid formulation. Polymeric amorphous solid dispersion(PASD) can greatly improve the apparent solubility and dissolution rate of poorly soluble drugs, has become a common technology to improve the oral bioavailability of poorly soluble drugs. However, due to the amorphous form of the drug at a high surface free energy in PASD, crystallization would occur during storage and dissolution, thereby losing its formulation advantages. The review attempts to provide a structural development approach of PASD products from the aspects of formulation and technology, in order to guide the development of stable and commercially viable PASD formulations. And the trend analysis of marketed products and patents of PASD will be discussed to understand the prospects of PASD's application in improving the bioavailability of poorly soluble oral solid formulations.

13.
Chinese Pharmaceutical Journal ; (24): 1450-1455, 2020.
Article in Chinese | WPRIM | ID: wpr-857600

ABSTRACT

OBJECTIVE: To prepare a ternary supersaturated indomethacin (IND) solid dispersion and investigate its characteristics by screening carrier materials with different functions based on quality by design (QbD) concept. METHODS: Based on dissolution tests, the carriers with solubilization function were selected and the appropriate drug loading ratio of binary solid dispersion was determined. The material as inhibitor of precipitation was chosen using the solvent shift method. The IND ternary supersaturated solid dispersion was prepared by the hot melt extrusion of IND, solubilization material and precipitation inhibitor. The dispersion state of IND was identified by differential scanning calorimetry and powder X-ray diffraction, and its characteristics were explored by the powder wettability test and the stability test. RESULTS: The binary IND solid dispersion with Eudragit EPO could sharply increase IND dissolution rate with a behavior of more than 80%dissolution within 5 min but subsequently followed an obvious concentration decline. Kollidon VA64 had a satisfactory effect of precipitation inhibition for IND supersaturated solution in that the concentration of 0.1% could keep the 50 μg•mL-1 IND solution unchanged within 30 min. The ternary solid dispersion with a mass ratio of 1:2:0.3 (IND:EPO:VA64) could significantly increase the dissolution of IND, eliminating the crystallization and precipitation of the drug in the supersaturated system during the dissolution process and enabling the drug to maintain amorphous form within 3 months. CONCLUSION: Based on the understanding of the functions of different carrier materials and the QbD concept, it could effectively improve the formulation design of solid dispersions. The prepared ternary IND solid dispersions have excellent drug dissolution behavior.

14.
Chinese Pharmaceutical Journal ; (24): 1401-1408, 2020.
Article in Chinese | WPRIM | ID: wpr-857592

ABSTRACT

Solid dispersions provide an effective technical method for improving solubility and bioavailability of insoluble drugs. From its discovery to the present 60 years, 26 drug formulations have been approved by FDA. Moreover, the preparation technology of solid dispersion system has been continuously innovated and developed, such as electrospinning method, supercritical fluid method, spray freeze-drying technology and so on. In this paper, the development process of solid dispersion technology and carrier is reviewed, and the development of solid dispersion technology and carrier is summarized, and the existing problems are analyzed and prospected. It is expected to provide the reference for the research and development of drug solid dispersion.

15.
China Pharmacy ; (12): 1054-1061, 2020.
Article in Chinese | WPRIM | ID: wpr-821493

ABSTRACT

OBJECTIVE:To prepare Cheler ythrine (CHE) solid dispe rsion (SD),optimize the formulation technology , characterize its preparation and investigate its in vitro antioxidant activity. METHODS :The content of CHE in SD was determined by UV spectrophotometry. Based on single factor tests ,using the product yield as index ,using preparation method ,carrier material type,carrier material proportion (drug-carrier material mass ratio )as factors ,the formulation technology of SD was optimized by L(9 34)orthogonal test and validated. Based on solubility and accumulative dissolution determination ,the product was characterized with thermal analyssis ,X-ray diffraction and scanning electron microscope. Using ascorbic acid as positive control ,in vitro antioxidant activity of the product was determined by DPPH method. RESULTS :The linear range of CHE was 2.4-5.6 μg/mL; quantitation limit and detection limit were 0.066 9,0.022 1 μg/mL;RSDs of precision ,stability and reproducibility tests were all lower than 2%;recoveries were 97.50%-99.25%(RSD<1%, n=3). The optimal preparation technology included using PEG 6000 as carrier material ,carrier material ratio of 1 ∶ 3, prepared by solvent method. Three batches of CHE-PEG-SD were prepared. Verification test results showed that the 话:0539-80311889。E-mail:zhenshengao@163.com accumulative dissolution of CHE-PEG-SD was (61.72 ± 0.67)% at 15 min,and the yield was (99.04±0.83)%. The results of characterization showed that after CHE-PEG-SD prepared , its solubility (3.725 mg/mL)and accumulative dissolution (61.25%,15 min)were higher than CHE raw material [ 0.098 mg/mL, 6.24%(180 min)]. The endothermic peak and crystal absorption peak moved or even disappeared compared with raw material and the carrier material ,and CHE was uniformly dispersed in the carrier material as an amorphous state. Results of in vitro antioxidation test showed that different concentration of CHE-PEG-SD showed certain ability of DPPH free radical scavenging ,and the IC 50 was 0.124 mg/mL,higher than 0.041 mg/mL of ascorbic acid. CONCLUSIONS :Established content determination method is simple and accurate. The optimal SD formulation technology is stable and feasible. The solubility of prepared CHE-PEG-SD increases,and the dissolution in vitro increases,showing certain in vitro oxidation resistance.

16.
Braz. J. Pharm. Sci. (Online) ; 56: e18641, 2020. tab, graf
Article in English | LILACS | ID: biblio-1132037

ABSTRACT

The aim of the present study was to enhance the dissolution rate of an NSAID drug Ketoprofen by formulating it into solid dispersions with water soluble carrier Poloxamer 188 and Eudragit S 100. The solid dispersions of Ketoprofen with Poloxamer 188 were prepared at 1:1, 1:1.5 and 1:2 (Ketoprofen: Poloxamer 188) ratio by Solvent evaporation methods. The same concentration ratio was used for the preparation of solid dispersion with Eudragit S 100 by melting/fusion technique. Further, solid dispersions were investigated by solubility, ATR-FTIR, XRD, DSC, surface morphology, in-vitro dissolution and accelerated stability study. Results demonstrated that both Poloxamer 188 and Eudragit S 100 improve solubility of drugs by 8­10 folds. The result of ATR-FTIR study showed the slight shifting/broadening of principle peaks. In vitro dissolution studies showed that in the solid dispersion system containing Ketoprofen: Poloxamer 188 batch P2 (1:1.5) gives faster dissolution rate of Ketoprofen than the physical mixtures. The solid dispersion with Eudragit S 100, batch E1 (1:1) gives faster dissolution rate of Ketoprofen than the physical mixtures. In phase solubility study with Poloxamer 188 showed concentration dependent solubilization of drug but Eudragit S 100 produced opposite result. The effect of pH on solubility of Eudragit S 100 was carried out which showed solubility at pH 7.4. The dissolution profile of solid dispersion with Eudragit S 100 at pH 7.4 gives excellent result. The Accelerated stability of solid dispersions & its physical mixtures were studied at 400±2 °C/75 ± 5% RH for a period of 1 month. In these studies, Solid Dispersion batches produced an unstable formulation. The Ketoprofen solid dispersions with Poloxamer 188 and Eudragit S 100 could be introduced as a suitable form with improved solubility


Subject(s)
Solubility , Ketoprofen/analogs & derivatives , Triage/classification , Poloxamer/analogs & derivatives , In Vitro Techniques , Pharmaceutical Preparations/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/classification , Spectroscopy, Fourier Transform Infrared , Dissolution/analysis , Hydrogen-Ion Concentration
17.
Article | IMSEAR | ID: sea-210480

ABSTRACT

The objective of the present investigation was to design and optimize lipid-based floating multiparticulate of Berberinehydrochloride (BERH), so as to increase its solubility and to reduce P-Glycoprotein mediated efflux in the intestine,hence to improve oral bioavailability. Solid dispersions were prepared using hydrophilic carriers gelucire 44/14and gelucire 50/13 in different ratio. The prepared solid dispersion of BERH was further formulated into sustainrelease gastroretentive floating pellets using hydrophobic lipid carrier gelucire 43/01 as release retardant, sodiumbicarbonate (NaHCO3) and hydroxylpropyl methyl cellulose K4M (HPMC K4M) as gas former and matrix polymer,respectively. The effect of amount of gelucire 43/01 and NaHCO3: HPMC K4M were studied and optimized using a3-level, 2-factor, factorial design. Solid dispersion of BERH compared to pure drug showed 4-fold enhancement inaqueous solubility. The optimum system could float for more than 8 hours and showed 88.46% drug release in 8 hours.The pharmacokinetic study conducted in male Wistar rats indicated 2.32-fold increase in relative bioavailability ofoptimized formulation compare to the marketed tablet. The lipid-based floating pellets of BERH were obtained andcould be an applicable choice to deliver BERH with improved bioavailability in effective use for various clinicalapplications.

18.
Article | IMSEAR | ID: sea-210441

ABSTRACT

The present work aims to enhance the water solubility of nimodipine, a hydrophobic drug, using a solid dispersion(SD) technique. Soluplus® as a novel hydrophilic polymeric carrier was used. Nimodipine-Soluplus® SDs (1:10) wereprepared by impregnation technique using supercritical fluid technology (SCF) and compared with the ones whichwere prepared by conventional hot-melt (HM) method. The solubility and the in vitro release study of the raw drug,solid dispersions, and the corresponding physical mixtures were characterized and compared. The prepared SD bySCF technology showed 77-fold increase in nimodipine solubility, in comparison to 48-fold increase when preparedby HM and 7.7-fold when physically mixed. Moreover, they showed the highest percentage of nimodipine cumulativerelease within the studied period. The results were confirmed the amorphous transfer of the drug into the polymermatrix which was assured by the powder X-ray diffraction and the thermal analysis. In addition to the hydrogen bondformation between nimodipine and Soluplus®, which was evident in the FTIR spectra; A weakening of peak related tonimodipine N–H stretching and C=O of the ester group. Nimodipine solid dispersion with Soluplus® using the SCFtechnology might represent a promising formulation for nimodipine to enhance its oral bioavailability

19.
Article | IMSEAR | ID: sea-206253

ABSTRACT

Efavirenz, a non-nucleotide reverse transcriptase inhibitor is an important drug for treating patients with Human Immunodeficiency Virus infections. It belongs to BCS class II have low solubility and poor intrinsic dissolution rate. It is highly basic (pKa 10.2) which makes it suitable candidate for floating dosage form for continuous delivery in stomach.The study was aimed to improve the solubility by solid dispersion technique.Saturation solubility study and drug content were evaluated for solid dispersion preparation. Saturation solubility shows 8 fold increases in 0.1 N HCL compared to plain drug and drug content was found to be between 95%-102%. Further effervescent floating gastroretentive drug delivery system was prepared by 32 full factorial design with independent variables i.e., concentration of HPMC K100 as matrix forming agent and citric acid as gas generating agent. Lag time, floating time, percent drug release were studied as responses. The optimized batch exhibited floating lag time of 40 sec and the in vitro release studies showed 89.5% drug release in 9 h and tablet remained floating for greater than 8 h. The study thus demonstrated that solubility is increased by solid dispersion technique and floating delivery systems may increase solubility and bioavailability of Efavirenz.

20.
Article | IMSEAR | ID: sea-206249

ABSTRACT

Oxcarbazepine has low solubility and low oral bioavailability, so it’s a challenge to formulate suitable dosage form. In this present investigation, to improve the dissolution rate and solubility, skimmed milk is used as a carrier. Physical mixers were prepared using various drugs to carrier ratio and spray drying technology was used to develop solid dispersion with the carrier. Various techniques were used to characterize the solid dispersion immediately after they were made which includes differential scanning calorimetry, scanning electron microscopy, fourier transform infra-red spectroscopy, X-ray diffraction and in-vitro dissolution profiles. The differential scanning calorimetry thermograms of raw drug indicated of its anhydrous crystalline nature. In thermograms of solid dispersion, the characteristic peak was absent suggesting the change from crystalline nature to amorphous form. X-ray diffraction confirmed those results. X-ray diffraction results of raw drug showed highly intense peak characteristic of its crystalline nature where solid dispersion showed less intense, more diffused peak indicating the change in crystalline form. Fourier transforms infra-red spectroscopy studies showed there was no interaction between drug and carrier. Scanning electron microscopy support the amorphous nature of mixer. The whole formulation showed distinct enhancement in the drug release behavior and solubility. The optimum oxcarbazepine to skimmed milk ratio 1:3 enhances the in-vitro drug release by 3.5 fold and also show distinct increase in solubility. It was concluded that for improvement of solubility of poorly water soluble oxcarbazepine, skimmed milk powder as a carrier can be utilize very well.

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