Orally disintegrating tablets (ODTs), also known as fast melts, quick melts, fast disintegrating and orodispersible systems, have the unique property of disintegrating in the mouth in seconds without ...chewing and the need of water and are thus assumed to improve patient compliance. Conventional methods like direct compression, wet granulation, moulding, spray-drying, freeze-drying and sublimation were used to prepare ODTs. New advanced technologies like Orasolv®, Durasolv®, Wowtab®, Flashtab®, Zydis®, Flashdose®, Oraquick®, Lyoc®, Advatab®, Frosta®, Quick-Disc® and Nanomelt® have been introduced by some pharmaceutical companies for the production of ODTs. The main objective of this review is to give a comprehensive insight into conventional and recent technologies used for the preparation of ODTs.
Oralno raspadljive tablete (ODT), poznate i kao lako topljive tablete, brzo raspadljive i kao orodisperzibilni sustavi, imaju jedinstveno svojstvo trenutnog raspadanja u ustima, bez žvakanja i bez potrebe uzimanja vode, što poboljšava pacijentovu suradljivost. U pripravi ODT koriste se uobičajene metode kao što su izravna kompresija, vlažna granulacija, kalupljenje, sušenje sprejanjem, sušenje smrzavanjem i sublimacija, a u njihovoj proizvodnji napredne tehnologije kao što su Orasolv®, Durasolv®, Wowtab®, Flashtab®, Zydis®, Flashdose®, Oraquick®, Lyoc®, Advatab®, Frosta®, Quick-Disc® i Nanomelt®. Cilj ovog rada je dati uvid u uobičajene i novije tehnologije u pripravi ODT.
Oralno raspadljive tablete (ODT), poznate i kao lako topljive tablete, brzo raspadljive i kao orodisperzibilni sustavi, imaju jedinstveno svojstvo trenutnog raspadanja u ustima, bez žvakanja i bez ...potrebe uzimanja vode, što poboljšava pacijentovu suradljivost. U pripravi ODT koriste se uobičajene metode kao što su izravna kompresija, vlažna granulacija, kalupljenje, sušenje sprejanjem, sušenje smrzavanjem i sublimacija, a u njihovoj proizvodnji napredne tehnologije kao što su Orasolv®, Durasolv®, Wowtab®, Flashtab®, Zydis®, Flashdose®, Oraquick®, Lyoc®, Advatab®, Frosta®, Quick-Disc® i Nanomelt®. Cilj ovog rada je dati uvid u uobičajene i novije tehnologije u pripravi ODT.
The objective of the present research was to develop a bilayer tablet of propranolol hydrochloride using superdisintegrant sodium starch glycolate for the fast release layer and water immiscible ...polymers such as ethylcellulose, Eudragit RLPO and Eudragit RSPO for the sustaining layer. In vitro dissolution studies were carried out in a USP 24 apparatus I. The formulations gave an initial burst effect to provide the loading dose of the drug followed by sustained release for 12 h from the sustaining layer of matrix embedded tablets. In vitro dissolution kinetics followed the Higuchi model via a non-Fickian diffusion controlled release mechanism after the initial burst release. FT-IR studies revealed that there was no interaction between the drug and polymers used in the study. Statistical analysis (ANOVA) showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p < 0.05) in the amount of drug released after 12 h from optimized formulations was observed.
U radu je opisan razvoj dvoslojnih tableta propranolol hidroklorida, koristeći superdezintegrator škrob glikolat natrij u sloju za brzo oslobađanje i polimere koji se ne miješaju s vodom (etilceluloza, Eudragit RLPO i Eudragit RSPO) u sloju za usporeno oslobađanje. In vitro oslobađanje praćeno je u USP aparatu I te je uočeno početno naglo oslobađanje ljekovite tvari iza kojeg slijedi polagano oslobađanje tijekom 12 sati. In vitro kinetika oslobađanja prati Higouchijev model, dok mehanizam kontroliranog oslobađanja ne slijedi Fickov zakon poslije početnog naglog oslobađanja. FT-IR studije ukazuju da nema interakcije između ljekovite tvari i polimera upotrebljenih u oblikovanju. Statistička analiza (ANOVA) nije pokazala značajne razlike u kumulativnoj količini oslobođenog lijeka iz optimiranih formulacija poslije 15 minuta, ali polije 12 h još se ta količina značajno razlikovala (p < 0.05).
Floating matrix tablets of norfloxacin were developed to prolong gastric residence time, leading to an increase in drug bioavailability. Tablets were prepared by the wet granulation technique, using ...polymers such as hydroxypropyl methylcellulose (HPMC K4M, HPMC K100M) and xanthan gum. Tablets were evaluated for their physical characteristics, viz., hardness, thickness, friability, and mass variation, drug content and floating properties. Further, tablets were studied for in vitro drug release characteristics for 9 hours. The tablets exhibited controlled and prolonged drug release profiles while floating over the dissolution medium. Non-Fickian diffusion was confirmed as the drug release mechanism from these tablets, indicating that water diffusion and polymer rearrangement played an essential role in drug release. The best formulation (F4) was selected based on in vitro characteristics and was used in vivo radiographic studies by incorporating BaSO4. These studies revealed that the tablets remained in the stomach for 180 ± 30 min in fasting human volunteers and indicated that gastric retention time was increased by the floating principle, which was considered desirable for the absorption window drugs.
Razvijene su plutajuće tablete norfloksacina koje se produljeno zadržavaju u želucu i time povećavaju bioraspoloživost. Tablete su pripravljene metodom vlažne granulacije, koristeći hidroksipropil metilcelulozu (HPMC K4M, HPMC K100M) i ksantan gumu. Tabletama su određena fizikalna svojstva (čvrstoća, debljina, lomljivost i varijacija mase) te sadržaj ljekovite tvari i plutajuća svojstva. Nadalje, praćeno je oslobađanje ljekovite tvari in vitro tijekom 9 h. Uočeno je da je oslobađanje kontrolirano i produljeno te da tablete plutaju u ispitivanom mediju. Mehanizam oslobađanja nije slijedio Fickov zakon, što ukazuje da difuzija vode i promjene u strukturi polimera imaju bitnu ulogu u oslobađanju ljekovite tvari. Najbolja formulacija (F4) in vitro uporabljena je za izradu pripravaka barijevog sulfata za radiografska ispitivanja in vivo. Ispitivanja na volonterima koji su apstinirali od hrane pokazala su da primjena plutajućih tableta produljuje vrijeme zadržavanja u želucu na 180 ± 30 min.
Buccoadhesive tablets of carvedilol were prepared using HPMC K4M, HPMC K15M and Carbopol 934 as mucoadhesive polymers. Fifteen formulations were developed with varying concentrations of polymers. ...Formulations of the BC or BD series were composed of HPMC K4M or HPMC K15M in ratios of 1:1 to 1:5 whereas in the BE series Carbopol 934 was used (1:0.25 to 1:1.50). The formulations were tested for in vitro drug release, in vitro bioadhesion, moisture absorption and in vitro drug permeation through porcine buccal mucosa. Formulation BC3 showed maximum release of the drug (88.7 ± 0.4%) with the Higuchi model release profile and permeated 21.5 ± 2.9% of the drug (flux 8.35 ± 0.291 μg h-1cm-2) permeation coefficient 1.34 ± 0.05 cm h-1) through porcine buccal membrane. BC3 formulation showed 1.62 ± 0.15 N of peak detachment force and 0.24 ± 0.11 mJ of work of adhesion. FTIR results showed no evidence of interaction between the drug and polymers. XRD study revealed that the drug is in crystalline form in the polymer matrix. The results indicate that suitable bioadhesive buccal tablets with desired permeability could be prepared.
Varirajući koncentracije bukoadhezivnih polimera HPMC K4M, HPMC K15M i Carbopol 934 pripravljeno je 15 tableta karvedilola. Pripravci iz serije BC ili BD izrađeni suiz karvedilola i HPMC K4 M ili HPMC K15M u omjerima 1:1, 1:2, 1:3, 1:4 i 1:5, a pripravci iz BE serije iz karvedilola i Carbopol 934 u omjerima 1:0.25, 1:0.50, 1:0.75, 1:1.00 i 1:1.50. In vitro je ispitivana brzina oslobađanja ljekovite tvari, bioadhezija, apsorpcija vlage i permeacija kroz bukalnu membranu svinje. Iz pripravka BC3 postignuto je maksimalno oslobađanje (88,7 ± 0,4%) koje je slijedilo Higuchijev model i maksimalna permeacija 21,5 ± 2,9% (fluks 8,35 ± 0,291 μg h-1 cm-2; permeacijski koeficijent 1,34 ± 0,05 cm h-1). Sila odvajanja za taj pripravak bila je 1,62 ± 0,15 N, a adhezija 0,24 ± 0,11 mJ. FTIR ispitivanja su pokazala da nije bilo interakcija između ljekovite tvari i polimera, a XRD ispitivanja da je ljekovita tvar u kristaliničnoj formi u polimernom matriksu. Pripravljene bukalne tablete su dovoljno bioadhezivne, a permeacija iz njih je zadovoljavajuća.
The purpose of this study was to improve the solubility and dissolution rate of carvedilol by forming a ternary complex with β-cyclodextrin and citric acid and to formulate its mouth-dissolving ...tablets. The rationale for preparing mouth-dissolving tablet of carvedilol was to make the drug available in a soluble form in the mouth, which would facilitate its absorption from the buccal cavity. This would help to overcome its first-pass metabolism and thereby improve bioavailability. Phase solubility studies revealed the ability of β-cyclodextrin and citric acid to complex with carvedilol and significantly increase its solubility. Ternary complexation of carvedilol was carried out with β-cyclodextrin and citric acid by physical mixing, kneading and spray drying methods and the prepared complexes were characterized by Fourier transform infra red spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, scanning electron microscopy and complexation efficiency. The complex obtained by the spray drying method resulted in highest complexation efficiency and a 110-fold increase in the solubility of carvedilol. The mouth-dissolving tablets formulated using the spray dried complex with suitable excipients showed 100 % dissolution within five minutes. Accelerated stability studies of mouth-dissolving tablets carried out as per ICH guidelines revealed that the tablets were stable.
Cilj rada bio je poboljšati topljivost i oslobađanje karvedilola stvaranjem ternarnog kompleksa s β-ciklodekstrinom i limunskom kiselinom i razvoj tableta topljivih u ustima. Takve tablete su napravljene s ciljem da se poboljša apsorpcija iz usta i izbjegne efekt prvog prolaza, što bi moglo imati za posljedicu poboljšanu bioraspoloživost. Testovi topljivosti pokazali su da β-ciklodekstrin i limunska kiselina stvaraju kompleks s karvedilolom i značajno povećavaju njegovu topljivost. Ternarna kompleksacija karvedilola s β-ciklodekstrinom i limunskom kiselinom provedena je fizičkim miješanjem, gnječenjem i sušenjem raspršivanjem. Pripravljeni kompleksi karakterizirani su infracrvenom spektroskopijom, diferencijalnom pretražnom kalorimetrijom, rendgenskom difraktometrijom praha, pretražnom elektronskom mikroskopijom i testovima učinkovitosti kompleksacije. Metodom sušenja raspršivanjem topljivost karvenidola povećala se 110 puta, a kompleksacija je bila najučinkovitija. Tablete pripravljene iz tog kompleksa i odgovarajućih pomoćnih tvari potpuno su se otopile unutar pet minuta. Testovi ubrzanog starenja provedeni prema ICH smjernicama pokazali su da su tablete stabilne.
Sildenafilcitrate (SILD) orodispersable sublingual tablets (ODSTs) have been developed using two comparative techniques for improving their oral disintegration, dissolution and bioavailability in ...order to manage acute attacks of pulmonary arterial hypertension (PAH). The techniques employed were direct compression of SILD-poloxamer 188 solid dispersions (SDs) and freeze drying using various excipients. The physicochemical and solid- -state properties, as well as the dissolution behavior of the tablets were evaluated. Moreover, SILD bioavailability in human volunteers from the prepared ODSTs was compared to that of the conventional oral tablet. Incorporation of SD of poloxamer188 in sublingual tablets together with Pharmaburst using the direct compression technique enhanced the extent and dissolution rate of SILD with 100 % of drug being dissolved after 7 minutes. However, the lyophilization process was superior in enhancing dissolution and 100 % of SILD was dissolved after only one minute. Moreover, the in vivo study showed that the AUC0-12 of lyophilized tablets was significantly higher than that of directly compressed tablets, with bioavailability values of 159.81 and 140.85 %, respectively, compared to the commercial oral product
U radu je opisan razvoj sublingvalnih tableta citrata (SILD) raspr{ivih u ustima (ODST) za terapiju plu}ne arterijske hipertenzije (PAH), sa svrhom pove}anja raspada nakon peroralne primjene, pove}anja osloba|anja i bioraspolo`ivosti. Primijenjena je metoda izravne kompresije ~vrstih disperzija (SD) sildenafila i poloksamera 188 i liofilizacija, a u izradi su upotrjebljena razli~ita pomo}na sredstva. Evaluirana su fizikokemijska svojstva te osloba|anje ljekovite tvari iz tableta. Osim toga, na dobrovoljcima je uspore-|ivana bioraspolo`ivost sildenafila iz ODST-a i standardnih tableta za peroralnu primjenu. Uklapanje SD poloksamera 188 u sublingvalne tablete uz Pharmaburst i kori{tenje izravne kompresije pove}alo je osloba|anje SILD-a tako da je nakon 7 minuta 100 % lijeka bilo otopljeno. Me|utim, liofilizacija se pokazala superiornom za pove}anje osloba- |anja jer se 100 % SILD-a oslobodilo nakon samo jedne minute. tovi{e, in vivo studije su pokazale da je AUC0-12 liofiliziranih tableta bila zna~ajno ve}a nego iz tableta dobivenih izravnim komprimiranjem, uz vrijednosti za bioraspolo`ivost od 159,81, odnosno 140,85 % u odnosu na komercijalno dostupne proizvode.
The purpose of the present research work was to observe the effects of drug solubility on their release kinetics of water soluble verpamil hydrochloride and insoluble aceclofenac from hydrophilic ...polymer based matrix formulations. Matrix formulations were prepared by the direct compression method. The formulations were evaluated for various physical parameters. Along with the dynamics of water uptake and erosion, SEM and in vitro drug release of the tablets were studied. Applying an exponential equation, it was found that the kinetics of soluble drug release followed anomalous non-Fickian diffusion transport whereas insoluble drug showed zero-order release. SEM study showed pore formation on the tablet surface that differed depending on drug solubility. t-Test pointed to a significant difference in amount of both drugs released due to the difference in solubility. Solubility of the drug effects kinetics and the mechanism of drug release.
Cilj rada bio je praćenje učinka topljivosti na kinetiku oslobađdanja vodotopljivog verapamil hidroklorida i netopljivog lijeka aceklofenaka iz matriksnih sustava na bazi hidrofilnog polimera. Matriksni sustavi pripravljeni su izravnom metodom kompresije. Uz ispitivanje uobičajenih fizikalnih svojstava, ispitivana je i dinamika primanja vode, te erozija, SEM i in vitro oslobađanje ljekovite tvari iz tableta. Primjenom eksponencijalne jednadžbe utvrđeno je da mehanizam oslobađanja topljivih lijekova slijedi anomalni ne-Fickov difuzijski transport, dok netopljivi lijekovi slijede kinetiku nultog reda. SEM ispitivanja pokazala su pore na površini matriksa ovisne o topljivosti ljekovite tvari. t-test ukazuje da količina oslobođenog lijeka značajno ovisi o njegovoj topljivosti. Topljivost lijeka ima značajan učinak na kinetiku i mehanizam oslobađanja.
The purpose of the present study was to develop an optimized gastric floating drug delivery system (GFDDS) containing domperidone as a model drug. Box-Behnken design was employed in formulating the ...GFDDS with three polymers: hydroxypropyl methylcellulose K4M (HPMC K4M) (X1), Carbopol 934P (X2) and sodium alginate (X3), as independent variables. Floating lag time (FLT), total floating time (TFT), time required to release 50% of the drug (t50) and diffusion exponent (n) were selected as dependent variables. Seventeen formulations were prepared, dissolution data obtained was fitted to the power law and floating profiles were analyzed. HPMC loading was found to be significant for floating properties. Carbopol loading had a negative effect on floating properties but was found helpful in controlling the release rate of the drug. No significant effect of sodium alginate on floating properties was observed but it was important for gel formation. The quadratic mathematical model developed could be used to predict formulations with desired release and floating properties.
Cilj rada bio je razvoj i optimizacija plutajućih sustava za isporuku lijekova u želucu (GFDDS) s domperidonom kao modelom lijeka. Box-Behnkenovo dizajniranje korišteno je u formuliranju GFDDS. Nezavisne varijable u dizajniranju bila su tri polimera: hidroksipropil metilceluloza K4M (HPMC K4M) (X1), Carbopol 934P (X2) i natrijev alginat (X3), a zavisne varijable usporeno vrijeme plutanja (FLT), ukupno vrijeme plutanja (TFT), vrijeme potrebno za oslobađanje 50% lijeka (t50) i difuzijski eksponent (n). Pripravljeno je ukupno sedamnaest formulacija. Analizirani su podaci o oslobađanju ljekovite tvari. Količina HPMC značajno utječe na svojstva plutanja, dok količina karbopola ima negativni učinak na svojstvo plutanja, ali kontrolira oslobađanje ljekovite tvari. Natrijev alginat nema značajni učinak na svojstva plutanja, ali utječe na stvaranje gela. Kvadratni matematički model može se upotrijebiti za predviđanje formulacija sa željenim profilom oslobađanja i svojstvima plutanja.
Tizanidine hydrochloride is an orally administered prokinetic agent that facilitates or restores motility through-out the length of the gastrointestinal tract. The objective of the present ...investigation was to develop effervescent floating matrix tablets of tizanidine hydrochloride for prolongation of gastric residence time in order to overcome its low bioavailability (34-40 %) and short biological half life (4.2 h). Tablets were prepared by the direct compression method, using different viscosity grades of hydroxypropyl methylcellulose (HPMC K4M, K15M and K100M). Tablets were evaluated for various physical parameters and floating properties. Further, tablets were studied for in vitro drug release characteristics in 12 hours. Drug release from effervescent floating matrix tablets was sustained over 12 h with buoyant properties. DSC study revealed that there is no drug excipient interaction. Based on the release kinetics, all formulations best fitted the Higuchi, first-order model and non-Fickian as the mechanism of drug release. Optimized formulation (F9) was selected based on the similarity factor (f2) (74.2), dissolution efficiency at 2, 6 and 8 h, and t50 (5.4 h) and was used in radiographic studies by incorporating BaSO4. In vivo X-ray studies in human volunteers showed that the mean gastric residence time was 6.2 ± 0.2 h.
Tizanidin hidroklorid je prokinetički agens za peroralnu primjenu koji olakšava ili obnavlja mobilnost kroz gastrointestinalni trakt. Cilj rada bio je razvoj šumećih plutajuć ih matriksnih tableta tizanidin hidroklorida za produljeno zadržavanje u želucu u svrhu poboljšanja niske bioraspoloživosti (34-40 %) i produljenja vremena poluživota (4,2 h). Tablete su pripravljene metodom izravne kompresije, koristeći hidroksipropil metilcelulozu različite viskoznosti (HPMC K4M, K15M i K100M). Određeni su različiti fizikalni parametri. Oslobađanje ljekovite tvari in vitro bilo je polagano tijekom 12 sati, a tablete su imale svojstvo plutanja. Prema DSC ispitivanja nema interakcije s pomoćnim tvarima. Kinetička ispitivanja pokazuju da oslobađanje iz svih pripravaka slijedi Higuchijev model, kinetiku prvog reda i ne-Fickov zakon. Na temelju faktora sličnosti (f2) (74,2), oslobađanja ljekovite tvari nakon 2, 6 i 8 h, te vremena poluživota t50 (5,4 h) izabrana je optimirana formulacija (F9) i upotrebljena u radiografičkim ispitivanjima koja uključuju BaSO4. In vivo ispitivanja rendgenskim zrakama na dobrovoljcima pokazala su da je srednje vrijeme zadržavanja u želucu bilo 6,2 ± 0,2 h.
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