When Interactions Between Bile Salts and Cyclodextrin Cause a Negative Food Effect: Dynamic Dissolution/Permeation Studies with Itraconazole (Sporanox®) and Biomimetic Media

The marketed oral solution of itraconazole (Sporanox®) contains 40% (259.2 mM) of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). The obvious role of HP-β-CD is to solubilize itraconazole and to overcome its poor aqueous solubility that restricts its absorption.In this study, we investigated the biorelevance of in vitro experiments by the influence of biomimetic media (containing bile salts and phospholipids) on the predicted itraconazole absorption from the commercial HP-β-CD-based Sporanox® solution. We performed phase-solubility studies of itraconazole and dynamic 2-step-dissolution/permeation studies using a biomimetic artificial barrier, Sporanox® solution, and fasted state simulated intestinal fluid (FaSSIF_V1).Both FaSSIF_V1 and HP-β-CD increased the apparent solubility of itraconazole when used individually. In combination, their solubility-enhancing effects were not additive probably due to the competition of bile salts with itraconazole for the hydrophobic cavity of HP-β-CD. Our combined dissolution/permeation experiments indicated the occurrence of a transient supersaturation from Sporanox® upon two-step dissolution. Through systematic variation of bile salt concentrations in the biomimetic media, it was observed that the extent and the duration of supersaturation depend on the concentrations of bile salts: supersaturation was rather stable in the absence of bile salts and phospholipids. The higher the bile salt concentration, the faster the collapse of the transient supersaturation occurred, an effect which is nicely mirrored by reduced in vitro permeation across the barrier. This is an indication of a negative food effect, which in fact correlates well with what earlier had been observed in clinical studies for Sporanox® solution.In essence, we could demonstrate that in vitro two-stage dissolution/permeation experiments using an artificial barrier and selected biomimetic media may predict the negative effects of the latter on cyclodextrin-based drug formulations like Sporanox® Oral Solution and, at the same time, provide a deeper mechanistic insight.     

羟丙基-β-环糊精包合对穿心莲内酯的增溶作用

目的研究羟丙基-β-环糊精(HP-β-CD)包合对穿心莲内酯(AND)溶解度和溶出度的增强作用。方法以HP-β-CD为载体,分别采用研磨法、超声波法和共沉淀法制备AND的HP-β-CD包合物,测定其溶出度和溶解度,并与AND原药、AND和HP-β-CD的物理混合物的溶出性能进行比较。结果 AND与HP-β-CD形成了包合物,HP-β-CD可使AND溶解度增加55.4倍。结论HP-β-CD极大地增加了AND的溶解度和溶出度。     

Enhancement of solubility and permeability of Candesartan cilexetil by using different pharmaceutical interventions

The poor solubility and wettability of Candesartan cilexetil (CAN) leads to poor dissolution and hence, low bioavailability after oral administration. The aim of the present study was to improve the solubility and dissolution rate and hence the permeability of CAN by preparing solid dispersions/inclusion complexes. Solid dispersions were prepared using PEG 6000 [hydrophilic polymer] and Gelucire 50/13 [amphiphilic surfactant] by melt agglomeration (MA) and solvent evaporation (SE) methods in different drug-to-carrier ratios, while inclusion complexes were made with hydroxypropyl-β-cyclodextrin (HP-β-CD) [complexing agent] by grinding and spray drying method. Saturation solubility method was used to evaluate the effect of various carriers on aqueous solubility of CAN. Based on the saturation solubility data, two drug-carrier combinations, PEG 6000 (MA 1:5) and HP-β-CD (1:1 M grinding) were selected as optimized formulations. FTIR, DSC, and XRD studies indicated no interaction of the drug with the carriers and provided valuable insight on the possible reasons for enhanced solubility. Dissolution studies showed an increase in drug dissolution of about 22 fold over the pure drug for PEG 6000 (MA 1:5) and 12 fold for HP-β-CD (1:1 M grinding). Ex-vivo permeability studies revealed that the formulation having the greatest dissolution also had the best absorption through the chick ileum. Capsules containing solid dispersion/ complex exhibited better dissolution profile than the marketed product. Thus, the solid dispersion/inclusion complexation technique can be successfully used for enhancement of solubility and permeability of CAN.     

羟丙基-β-环糊精对兰索拉唑的增溶作用及其包合物的制备

目的研究羟丙基-β-环糊精(HP--βCD)对难溶性药物兰索拉唑(LPZ)的包合作用。方法绘制相溶解度图,考察pH变化、碳酸氢钠的加入对LPZ的增溶作用。采用共蒸发法(CE)和喷雾干燥法(SD)按照LPZ∶HP--βCD量比为1∶1或1.0∶1.5的比例制备LPZ/HP--βCD包合物,测定其溶出度,并利用差示扫描量热法(DSC)和傅立叶红外光谱法(FTIR)对SD法制备的包合物进行结构表征。结果在pH 11条件下,HP-β-CD与NaHCO3对LPZ的协同增溶效果最好。体外溶出实验表明:CE法和SD法制备的包合物溶出均优于LPZ与HP-β-CD的物理混合物。结论HP--βCD能明显提高LPZ的溶解度和溶出度。     

Preparation,characterization, dissolution,and permeation of flibanserin − 2-HP-β-cyclodextrin inclusion complexes

Flibanserin (FLB), an antiserotonin drug, is used to treat women with hypoactive sexual appetite disorder. FLB shows low bioavailability (~33%) probably due to its low water solubility. The current study investigated the impact of hydroxypropyl-β-cyclodextrin (HP-β-CD) and sodium lauryl sulfate (SLS) on the dissolution and permeation of FLB. HP-β-CD–FLB inclusion complexes were prepared using physical mixing and kneading at 1:1 and 1:2 M ratios and characterized using differential scanning calorimetry, Fourier transform infrared spectroscopy, and powder X-ray diffractometry. The dissolution and permeation of the complexes through a cellophane membrane were performed in, 0.1, 0.3 and 0.5% SLS in phosphate buffer (pH 6.8).Derived from the slope of the linear phase solubility diagram, the apparent stability constant (K_1:1) was 372.54 M⁻¹. Kneading changed the crystalline form of FLB to an amorphous appearance characterized by minimal crystalline peaks, indicating successful inclusion complex formation. In addition, the HP-β-CD–FLB inclusion complexes showed twofold increased dissolution efficiency at 6 h. The cumulative FLB amount permeated at 6 h increased from 14.1% to 21.88% and 34.56% in the presence of 0.1% and 0.3% of SLS, respectively. However, increasing SLS to 0.5% did not show an increase in FLB permeation. Therefore, the HP-β-CD–FLB inclusion complex has an improved dissolution rate compared to FLB alone. The presence of SLS in the dissolution medium increases the dissolution rate of pure FLB and its complex with HP-β-CD. kneaded 1:1 complex was formulated bioadhesive buccal tablets and showed enhanced drug release.     

Inclusion complexes of tadalafil with natural and chemically modified β-cyclodextrins. I: Preparation and in-vitro evaluation

The aim of this work was to investigate the inclusion complexation between tadalafil, a practically insoluble selective phosphodiesterase-5 inhibitor (PDE5), and two chemically modified β-cyclodextrins: hydroxypropyl-β-cyclodextrin (HP-β-CD) and heptakis-[2,6-di-O-methyl]-β-cyclodextrin (DM-β-CD), in comparison with the natural β-cyclodextrin (β-CD) in order to improve the solubility and the dissolution rate of the drug in an attempt to enhance its bioavailability. Inclusion complexation was investigated in both the solution and the solid state. The UV spectral shift method indicated guest–host complex formation between tadalafil and the three cyclodextrins (CDs). The phase solubility profiles with all the used CDs were classified as A_p-type, indicating the formation of higher order complexes. The complexation efficiency values (CE), which reflect the solubilizing power of the CDs towards the drug, could be arranged in the following order: DM-β-CD > HP-β-CD > β-CD. Solid binary systems of tadalafil with CDs were prepared by kneading and freeze-drying techniques at molar ratios of 1:1, 1:3 and 1:5 (drug to CD). Physical mixtures were prepared in the same molar ratios for comparison. Physicochemical characterization of the prepared systems at molar ratio of 1:5 was studied using differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and Fourier-transform infrared spectroscopy (FTIR). The results showed the formation of true inclusion complexes between the drug and both HP-β-CD and DM-β-CD using the freeze-drying method at molar ratio of 1:5. In contrast, crystalline drug was detectable in all other products. The dissolution of tadalafil from all the prepared binary systems was carried out to determine the most appropriate CD type, molar ratio, and preparation technique to prepare inclusion complexes to be used in the development of tablet formulation for oral delivery of tadalafil. The dissolution enhancement was increased on increasing the CD proportion in all the prepared systems. Both the CD type and the preparation technique played an important role in the performance of the system. Irrespective of the preparation technique, the systems prepared using HP-β-CD and DM-β-CD yielded better performance than the corresponding ones prepared using β-CD. In addition, the freeze-drying technique showed superior dissolution enhancement than other methods especially when combined with the β-CD derivatives.     

A donepezil/cyclodextrin complexation orodispersible film: Effect of cyclodextrin on taste-masking based on dynamic process and in vivo drug absorption

The aim of this study was to develop a palatable donepezil (DP) orodispersible film (ODF) to facilitate the swallowing process and investigate the effect of cyclodextrin on taste-masking based on dynamic process and in vivo drug absorption. Complexation of DP with hydroxypropyl-β-cyclodextrin (HP-β-CD) was applied to mask the bitter taste then the prepared complexes were incorporated into ODF using solvent casting method. The taste-masking efficiency was evaluated by e-tongue; meanwhile the pharmacokinetic behavior of DP/HP-β-CD ODF was investigated by in vivo study. Results showed the optimized film was more palatable than donepezil hydrochloride (DH) film and was bioequivalent with DH. The molecular mechanism was revealed by phase solubility study, Fourier-transform infrared spectrometer (FT-IR), Differential scanning calorimeter (DSC), X-ray diffraction (XRD) and molecular modeling. Taste-masking was attributed to the formation of DP/HP-β-CD which was due to moderate interaction between DP and HP-β-CD. The stability of DP/HP-β-CD was decreased because of the acid environment in stomach, which facilitated the absorption of DP. These results extended our understanding about the application of cyclodextrin complexation and provided guidance for the design of ODF especially for drugs with disgusting taste.     

伊曲康唑包合物注射液的制备及理化性质考察

目的制备伊曲康唑注射液并考察其理化性质。方法以羟丙基β环糊精(HP βCD)为增溶剂,采用溶液 搅拌法制备伊曲康唑包合物注射液,采用HPLC法测定伊曲康唑的含量。结果HP βCD对药物具有较好的增溶作用,伊曲康唑注射液的pH值、渗透压、澄明度等性质均符合要求。结论伊曲康唑包合物注射液符合《中华人民共和国药典》注射剂质量标准     

卡维地洛羟丙基-β-环糊精包合物的制备与评价

目的制备卡维地洛羟丙基-β-环糊精包合物,对包合物进行物性研究。方法采用超声法制备包合物,通过相溶解度研究包合类型,以差示扫描热分析法(DSC)和X-射线衍射法验证卡维地洛羟丙基-β-环糊精包合物的形成,并测定包合物的溶解度和溶出度。结果相溶解度曲线呈AL型,表明卡维地洛能够与羟丙基-β-环糊精形成1∶1的包合物。DSC和X-射线衍射结果显示药物峰消失,证明包合物的形成。包合物的溶解度比原药提高5倍,溶出速度明显加快。结论超声法制备的卡维地洛羟丙基-β-环糊精包合物能显著提高原药的溶解度和溶出速度。     

Alginate-Based Hydrogel Containing Minoxidil/Hydroxypropyl-β-Cyclodextrin Inclusion Complex for Topical Alopecia Treatment

Cutaneous minoxidil (MXD) formulations were developed with the intent to reduce the side effects of the cosolvents propylene glycol and ethanol, frequently used in commercial MXD solutions. Completely aqueous alginate-based hydrogels were investigated and MXD aqueous solubility was improved using inclusion complexes with hydroxypropyl-β-cyclodextrin (HP-β-CD) at 2 different molar substitution degree (MS), namely 0.65 and 0.85. HP-β-CD MS 0.65 was selected for its improved solubilizing ability toward MXD. At concentration of 39% w/v, this cyclodextrin increased the intrinsic aqueous solubility of MXD of about 22-fold. The calculated complexation constant was 2309 ± 20 M^?1, and the inclusion process was spontaneous and enthalpically driven. Nuclear magnetic resonance studies (Job plot, ¹H, 2D correlations spectroscopy, nuclear overhauser effect spectroscopy, and rotating-frame overhauser enhancement spectroscopy) confirmed the stoichiometry 1:1 between MXD and HP-β-CD providing information about the exact geometry of the inclusion complex. Rheological and in vitro release studies performed on the formulation loaded with MXD 3.5% w/w proved that the inclusion complex increased the viscosity of the hydrogel modulating the release of the free drug. Furthermore, the hydrogel formulation facilitate MXD to permeate into the skin and did not damage epidermis, suggesting that these completely aqueous MXD delivery systems can be proposed as alternative formulations to commercial solutions.     

Development of orally disintegrating tablets of Perphenazine/hydroxypropyl-β-cyclodextrin inclusion complex

The aim of the present work was to prepare perphenazine (PPZ) orally disintegrating tablets (ODTs) based on the use of hydroxypropyl-β-cyclodextrin (HP-β-CD) forming inclusion complex with PPZ to improve the solubility and dissolution of this practically insoluble drug. Phase solubility studies were performed to evaluate the complexation of PPZ with HP-β-CD in three aqueous systems. The inclusion complex prepared by evaporation method was characterized by different physicochemical techniques, including the dissolution studies. The prepared complex was incorporated into ODTs containing different fillers and disintegrants. The ODTs prepared by direct compression were evaluated for drug content, hardness, porosity, friability, in vitro disintegration time (DT), wetting time (WT) and dissolution profiles. The solubility and dissolution rate were substantially improved compared with that of PPZ. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR) analyses suggested that PPZ could form true inclusion complex with HP-β-CD. The optimized formulation F6 exhibited short DT (15.5 ± 1.9 s) and WT (34.2 ± 2.3 s), sufficient hardness (30.4 ± 1.6 N/mm) and rapid drug dissolution. The developed tablet formulation could be a promising drug delivery system with improvements in PPZ bioavailability and patient compliance.     

In Vitro Tools for Evaluating Novel Dosage Forms of Poorly Soluble,Weakly Basic Drugs: Case Example Ketoconazole

The aim of the present series of experiments was to compare various in vitro tools including evaluation of formulations influence on solubility, various dissolution tests, and an updated, miniaturized transfer model to forecast the behavior of novel formulations of the poorly soluble, weakly basic model compound ketoconazole (KETO) after oral administration. A binary complex with hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) and a ternary formulation with HP‐β‐CD and Soluplus® were evaluated and their solubility, dissolution, and transfer behavior was compared with that of the pure drug. Binary and ternary formulations could significantly improve (p < 0.05) KETO solubility in all test media. Dissolution in media simulating the fasted stomach and the fed small intestine was almost complete for the pure drug and both complex formulations. By contrast, in pH 6.5 FaSSIF, dissolution of the pure drug was less than 10%. Both formulations resulted in significantly higher KETO release (p < 0.05) in this test medium (32%/95% release from the binary/ternary formulation). In the transfer experiments, the ternary complex showed the best performance with respect to stabilizing a supersaturated solution and inhibiting precipitation of KETO. Overall, the miniaturized transfer model appeared to be the best single tool for rank‐ordering formulations.     

羟丙基-β-环糊精与介质pH值对前列腺素E_1溶解度的综合影响（英文）

目的研究羟丙基-β-环糊精（HP-β-CD）与介质pH值对前列腺素E1（PGE1）溶解度的综合影响并进一步推导出该药物溶解度的理论方程。方法首先测定药物在不同pH值水中的溶解度;然后分别测定在酸性及中性系列浓度的HP-β-CD溶液中,药物的溶解度;最后推导出以HP-β-CD与介质pH值为变量的药物溶解度方程并对其合理性进行验证。结果溶解度测定结果表明,提高介质的pH值或以HP-β-CD为增溶剂,均可增加PGE1的溶解度。分子型药物或离子型药物与HP-β-CD测得的相溶解度图均为典型的AL型,提示药物结构上的五元碳环部分已嵌入HP-β-CD的疏水性孔穴中,从而形成1：1摩尔比包合物。结论以HP-β-CD作为增溶剂,同时提高介质的pH值,可对PGE1的溶解度产生协同增加效应。本研究中导出的PGE1溶解度方程,可有效表征HP-β-CD与介质pH值二者对该药物溶解度的综合影响。     

Physicochemical characterization and dissolution of norfloxacin/cyclodextrin inclusion compounds and PEG solid dispersions

Increase in the poor water solubility and dissolution rate of norfloxacin was studied. Two systems were used: solid dispersion with PEG 6000 prepared using the fusion method and inclusion complexes with cyclodextrins (β-cyclodextrin and HP-β-cyclodextrin) obtained by freeze-drying. IR spectrophotometry, X-ray diffractometry, and differential scanning calorimetry showed differences between norfloxacin/cyclodextrin complexes and their corresponding physical mixtures, but not between norfloxacin/PEG 6000 solid dispersions and their corresponding physical mixtures. The solubility and dissolution rate of norfloxacin were significantly increased with PEG solid dispersions and cyclodextrin complexes as well as with norfloxacin-CD physical mixtures. However, enhancement was not statistically different either among various cyclodextrin complexes, or between solid dispersions and cyclodextrin complexes.     

Physicochemical evaluation and in vitro release studies on itraconazolium sulfate salt

To counter the poor aqueous solubility of itraconazole (ITC), its sulfate salt (ITCSUL) was synthesized and characterized by ¹H NMR, MS, FTIR, DSC, XRPD, DLS and SEM. Antifungal properties of ITCSUL were confirmed against different fungal pathogens by broth microdilution method. Enhanced solubility of the salt in various pharmaceutical solvents was observed. Approximately 5.5 fold increase in percentage drug release from ITCSUL than that of ITC in 3 h was observed. Further, the physical mixtures of ITCSUL with two cyclodextrins; β-cyclodextrin (β-CD) and HP-β-cyclodextrin (HP-β-CD) were prepared in 3 M ratios. The in vitro release studies of CD mixtures of ITC and ITCSUL exhibited markedly enhanced dissolution in comparison to ITC and ITCSUL respectively. The promising in vitro performance of ITCSUL and ITCSUL CD mixtures along with advantage of expedient preparation suggest their potential applications in designing a better oral drug delivery system.     

Drug product development and pharmacological evaluation of a sparingly soluble novel camptothecin analog for peroral administration

This work focused on the developmental aspects, pharmacokinetic evaluation, and pharmacological assessment of a drug inclusion complex for a novel camptothecin analog (CA) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). Camptothecins analog belong to topoisomerase-I inhibitor class of compounds with proven anti-tumor activity but exhibit poor solubility. To enhance solubility a drug inclusion complex with cyclodextrin was developed using a spray-drying process. The powder complex characterized using DSC, XRPD, FT-IR, and ¹H NMR techniques confirmed interaction of cyclodextrin with the CA indicating formation of a true complex wherein the drug is encapsulated in the cyclodextrin cavity. The saturation solubility and dissolution kinetics of drug complex evaluated in a discriminating medium showed significantly higher solubility and faster dissolution as compared to a physical mixture or powder blend comprising of drug and cyclodextrin. Pharmacokinetic (PK) studies in Wistar rats indicated a significant increase in the rate and extent of absorption for the drug complex as compared to a nanoparticulate dispersion that was used as the positive control. Pharmacological activity following peroral administration of drug complex in athymic nude mice with implanted tumors revealed that the tumor inhibition activity was equivalent to commercially available intravenous (IV) formulation with comparable safety profile. These studies demonstrated for the first instance feasibility of developing a safe and efficacious peroral formulation for a sparingly soluble camptothecin analog that may provide another viable, patient compliant, and cost effective option for the treatment of solid tumors.     

Drug product development and pharmacological evaluation of a sparingly soluble novel camptothecin analog for peroral administration

This work focused on the developmental aspects, pharmacokinetic evaluation, and pharmacological assessment of a drug inclusion complex for a novel camptothecin analog (CA) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). Camptothecins analog belong to topoisomerase-I inhibitor class of compounds with proven anti-tumor activity but exhibit poor solubility. To enhance solubility a drug inclusion complex with cyclodextrin was developed using a spray-drying process. The powder complex characterized using DSC, XRPD, FT-IR, and 1H NMR techniques confirmed interaction of cyclodextrin with the CA indicating formation of a true complex wherein the drug is encapsulated in the cyclodextrin cavity. The saturation solubility and dissolution kinetics of drug complex evaluated in a discriminating medium showed significantly higher solubility and faster dissolution as compared to a physical mixture or powder blend comprising of drug and cyclodextrin. Pharmacokinetic (PK) studies in Wistar rats indicated a significant increase in the rate and extent of absorption for the drug complex as compared to a nanoparticulate dispersion that was used as the positive control. Pharmacological activity following peroral administration of drug complex in athymic nude mice with implanted tumors revealed that the tumor inhibition activity was equivalent to commercially available intravenous (IV) formulation with comparable safety profile. These studies demonstrated for the first instance feasibility of developing a safe and efficacious peroral formulation for a sparingly soluble camptothecin analog that may provide another viable, patient compliant, and cost effective option for the treatment of solid tumors.     

Soluplus® as an effective absorption enhancer of poorly soluble drugs in vitro and in vivo

As many new active pharmaceutical ingredients are poorly water soluble, solubility enhancers are one possibility to overcome the hurdles of drug dissolution and absorption in oral drug delivery. In the present work a novel solubility enhancing excipient (Soluplus®) was tested for its capability to improve intestinal drug absorption. BCS class II compounds danazol, fenofibrate and itraconazole were tested both in vivo in beagle dogs and in vitro in transport experiments across Caco-2 cell monolayers. Each drug was applied as pure crystalline substance, in a physical mixture with Soluplus®, and as solid solution of the drug in the excipient. In the animal studies a many fold increase in plasma AUC was observed for the solid solutions of drug in Soluplus® compared to the respective pure drug. An effect of Soluplus® in a physical mixture with the drug could be detected for fenofibrate. In vitro transport studies confirm the strong effect of Soluplus® on the absorption behavior of the three tested drugs. Furthermore, the increase of drug flux across Caco-2 monolayer is correlating to the increase in plasma AUC and C_max in vivo. For these poorly soluble substances Soluplus® has a strong potential to improve oral bioavailability. The applicability of Caco-2 monolayers as tool for predicting the in vivo transport behavior of the model drugs in combination with a solubility enhancing excipient was shown. Also the improvement of a solid dispersion compared to physical mixtures of the drugs and the excipient was correctly reflected by Caco-2 experiments. In the case of fenofibrate the possible improvement by a physical mixture was demonstrated, underscoring the value of the used tool as alternative to animal studies.     

Transdermal delivery of the in situ hydrogels of curcumin and its inclusion complexes of hydroxypropyl-β-cyclodextrin for melanoma treatment

Curcumin (Cur) is a hydrophobic polyphenol with diverse pharmacological effects, especially for cancer treatment. However, its weak water solubility and stability was the major obstacle for the formulation research of Cur. The complexation of Cur and hydroxypropyl-β-cyclodextrin (HP-β-CD) was done by grinding. The increasing solubility of Cur was achieved due to complexation and the photochemical stability of Cur was improved. The inclusion of Cur could happen when two ends of Cur were embedded into the cavity of the HP-β-CD rings. The in situ hydrogels (ISGs) of Cur and its inclusion complexes were prepared using poloxamers 407 and 188 as the matrix. The extent of drug’s in vitro release from the ISGs depended on the dissolution of drugs. Both of the ISGs had transdermal effect and cytotoxicity on B16-F10 cells. However, the effects of the ISGs containing Cur inclusion complexes were much higher than those of Cur ISGs because of the improved Cur solubility in the former. The cytotoxicity of Cur on melanoma cells was related to blocking of cellular proliferation in the G₂/M stage followed by cellular apoptosis. The ISGs of Cur inclusion complexes are a promising formulation for melanoma treatment.     

Preparation,characterization, and antibacterial activity of plaunotol and plaunoi extracts complexed with hydroxypropyl-β-cyclodextrin

Croton stellatopilosus (Plaunoi) leaves accumulate several diterpenes and possess various pharmacological activities. The present study aimed to prepare, characterize and assess the antibacterial activity of inclusion complexes prepared by mixing plaunotol (PL) or plaunoi extract (PE) with cyclodextrins (CD), including α-CD, β-CD, γ-CD, and hydroxypropyl-β-cyclodextrin (HP-β-CD). The inclusion complexes were characterized using SEM, XRD, DSC, and FT-IR and evaluated for aqueous solubility and thermal stability. The PL and PE lyophilized complexes with HP-β-CD were further evaluated for their antibacterial activity against acne-causing bacteria. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of PL, PE, and the inclusion complexes evaluated using the agar dilution method revealed that the MIC and MBC values of the inclusion complexes were lower than those of PL or PE alone. Interestingly, the complexes had a synergistic activity with clindamycin after testing with checkerboard assay. The hydrogel containing the inclusion complex and clindamycin were assessed for antibacterial activity using the agar well diffusion method. The results indicated that the hydrogels showed significant inhibition of bacterial growth. In conclusion, the prepared solid dispersion of PL or PE with HP-β-CD could enhance antibacterial activity by increasing the drug solubility. The hydrogels containing PL or PE complex and clindamycin could be considered as a candidate for the treatment of acne vulgaris.