Study On The Preparation Of Acyclovir - Hydrotalcite Intercalation Compound

A layered doubled hydroxide(LDH)nanocomposite vehicle for acyclovir(ACV)was designed and prepared to control the drug release rate.The inorganic Mg-Al-layered double hydroxide was used as matrix.ACV,an antivirus drug was hosting as model drug.The effective to characterization of the composites by using different methods were evaluated.Three different methods,spray-dried,complex coacervation and solvent-nonsolvent were adopted to prepare the microcapsule.The characterization of the microcapsule was studied preliminarily.A HPLC method was established to determine the content of ACV,which was simple and specific.Through the stability experiment,ACV is stable at pH 4.5 to 9.8 in buffer solution,but would degradation quickly when pH is over 11.However,LDH is instability under low pH condition.The process of preparation of LDH-ACV composites is also need higher pH. Therefore,pH of the reaction should be kept from 8 to 11 to prevent ACV from degradation.An orthogonal experiment was designed to investigate effective of temperature,pH,time for crystal and radio of LDH and ACV.There are three different methods to prepare the LDH-ACV composites,ion-exchanged,calcined-recuperation and co-precipitated.The comparison among the three methods was carried to choose the best one.Meanwhile,drug loading capacity and percentage release in vitro were employed to evaluate the quality of the composites.XRD,FT-IR and SEM were used to observe the crystal pattern and appearance of microparticles.In all,the drug loading capacity of composites prepared using ion-exchanged method was the lowest,64.916 mg·g^-1(calcined-recuperation)and 7.135 mg·g^-1 (co-precipitation),respectively.The release process consisted of four periods:an initial stage of a very rapid burst,because some of the drug may be absorbed on the surface of LDH;a second stage with a stable but much slower rate,ions in the solution exchanged with ACV- in the interlayer;a third period with almost no release,may be caused by the depletion of anions in the hierarchy and the balance of anions exchanged;and a final stage in which the release was a little faster than before.Since the powder was present in the liquid for a long enough time,H₂O and anions entered the lamellar structure of LDH,and the interlayer space became bigger. Consequently,with the collapse of the lamellar structure of LDH,ACV rapidly passed into solution.Composites prepared by calcined-recuperation were complex to prepare.Therefore, composites prepared by co-precipitated method were adopted for further investigation.The formulation was set as follow:LDH 10g,ACV 0.3g,acid q.s.,NaOH q.s.There is a significant difference between the drug-loading capacity of composites prepared by calcined-recuperation method and co-precipitation method.So it is possible that when adopted co-precipitated method,the effective of using different anions during preparation was evaluated.The difference among the composites was studied via its drug release property and characterization,such as XRD,FT-IR and SEM.The drug loading capability of the LDH nanocomposite was 12.04 mg·g^-1(Cl^-),12.86 mg·g^-1(NO₃^-),6.93 mg·g^-1(SO₄^2-)and 8.52 mg·g^-1 (AC^-),respectively.Compared the composites(SO₄^2-)with other composites,both drug release property and characterization show great difference..However,composite prepared using HAC, which shows best release curve,was chosen as core material.LDH,a kind of alky compound,is not stabile in acor media,and will dissolve immediately under the pH condition lower than 5.It is necessary to encaspsule the composites into enterosoluble capsule wall material so as to prevent the drug release instantly.Comparison among spray-dried,complex coacervation and solvent-nonsolvent were carried out.It is shown that diameter of microcapsule prepared by complex coacervation is too large,microcapsule prepared by solvent-nonsolvent is easily to agglomerate,microcapsule prepared by spray-dried is good.An orthogonal experiment was designed to test the effective of procedure.The preparation condition was:aspiration flow:40,inlet temperature:120℃,radio(capsule wall material:core material):4:1.The microcapsule using Polyoxylateâ…¡as capsule wall material has a good flow ability. However,microcapsules using algin as capsule wall material show bad flow ability.All the microcapsules are with good acid fastness.The release curve of microcapsules correlates to the viscosity of algin,as the viscosity increased,the release rate decreased.However,the release curve of the microcapsule which uses LF240D as capsule wall material was similar to composite. The release rate in pH=6.0 media is higher than in pH=5.0,and in pH=6.8 is the highest of all. Apparent morphous of microcapsule was observed by SEM.It is shown that all the microcapsule was round,like ball,but peplos of microcapsule using LF240D as capsule wall material was not continual.